Author: "Berkhout, Ben" / Database: OpenAIRE - Searchworks@Jio Institute Digital Library Search Results

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61 results on '"Berkhout, Ben"'

1. HIV-phyloTSI: Subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data

Author: Golubchik, Tanya, Abeler-Dörner, Lucie, Hall, Matthew, Wymant, Chris, Bonsall, David, Macintyre-Cockett, George, Thomson, Laura, Baeten, Jared, Celum, Connie, Galiwango, Ronald, Kosloff, Barry, Limbada, Mohammed, Mujugira, Andrew, Mugo, Nelly, Gall, Astrid, Blanquart, François, Bakker, Margreet, Bezemer, Daniela, Ong, Swee Hoe, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych, Kivelä, Pia, Kouyos, Roger, Meyer, Laurence, Porter, Kholoud, van Sighem, Ard, van der Valk, Mark, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Ayles, Helen, Burns, David, Fidler, Sarah, Grabowski, Mary Kate, Hayes, Richard, Herbeck, Joshua, Kagaayi, Joseph, Kaleebu, Pontiano, Lingappa, Jairam, Ssemwanga, Deogratius, Eshleman, Susan, Cohen, Myron, Ratmann, Oliver, Laeyendecker, Oliver, Fraser, Christophe, Blanquart, François, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and On behalf of the HPTN 071 (PopART) Phylogenetics protocol team, the BEEHIVE collaboration and the PANGEA consortium
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining duration of infection classify samples into recent and non-recent and are unable to give more granular TSI estimates. These binary classifications have a limited recency time window of several months, therefore requiring large sample sizes, and cannot assess the cumulative impact of an intervention. We developed a Random Forest Regression model, HIV-phyloTSI, that combines measures of within-host diversity and divergence to generate TSI estimates from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performed equally well for all major HIV subtypes based on data from African and European cohorts. We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.
Published: 2022

2. Correction: HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry (Journal of Biological Chemistry (2019) 294(15) (5736–5746), (S0021925820366424), (10.1074/jbc.RA119.007360))

Author: Eggink, Dirk, Bontjer, Ilja, de Taeye, Steven W., Langedijk, Johannes P. M., Berkhout, Ben, Sanders, Rogier W., Medical Microbiology and Infection Prevention, AII - Infectious diseases, and AII - Inflammatory diseases
Abstract: Funding and additional information should read as follows: This work was supported by Aids Fonds Netherlands Grants 2005021 and 2008013, the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) Grants OPP1111923 and OPP1132237, National Institutes of Health Grant P01 AI110657 and funding from European Union's Horizon 2020 research and innovation programme under grant agreement No 681137.
Published: 2022

3. A highly virulent variant of HIV-1 circulating in the Netherlands

Author: Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, Gall, Astrid, Hall, Matthew, Golubchik, Tanya, Bakker, Margreet, Ong, Swee Hoe, Zhao, Lele, Bonsall, David, de Cesare, Mariateresa, MacIntyre-Cockett, George, Abeler-Dörner, Lucie, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F, Kivelä, Pia, Kouyos, Roger D, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B Martinez, Marzolini, C, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Weber, R, Yerly, S, van der Valk, M, Geerlings, S E, Goorhuis, A, Hovius, J W, Lempkes, B, Nellen, F J B, van der Poll, T, Prins, J M, Reiss, P, van Vugt, M, Wiersinga, W J, Wit, F W M N, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A M H, Pijnappel, F J J, Smalhout, S Y, Weijsenfeld, A M, Jurriaans, S, Back, N K T, Zaaijer, H L, Berkhout, B, Cornelissen, M T E, Schinkel, C J, Wolthers, K C, Peters, E J G, van Agtmael, M A, Autar, R S, Bomers, M, Sigaloff, K C E, Heitmuller, M, Laan, L M, Ang, C W, van Houdt, R, Jonges, M, Kuijpers, T W, Pajkrt, D, Scherpbier, H J, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Buiting, A, Reuwer, A, Veenemans, J, Wintermans, B, Pronk, M J H, Ammerlaan, H S M, van den Bersselaar, D N J, de Munnik, E S, Deiman, B, Jansz, A R, Scharnhorst, V, Tjhie, J, Wegdam, M C A, van Eeden, A, Nellen, J, Brokking, W, Elsenburg, L J M, Nobel, H, van Kasteren, M E E, Berrevoets, M A H, Brouwer, A E, Adams, A, van Erve, R, de Kruijf-van de Wiel, B A F M, Keelan-Phaf, S, van der Ven, B, Buiting, A G M, Murck, J L, de Vries-Sluijs, T E M S, Bax, H I, van Gorp, E C M, de Jong-Peltenburg, N C, de Mendonç A Melo, M, van Nood, E, Nouwen, J L, Rijnders, B J A, Rokx, C, Schurink, C A M, Slobbe, L, Verbon, A, Bassant, N, van Beek, J E A, Vriesde, M, van Zonneveld, L M, de Groot, J, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Fraaij, P L A, van Rossum, A M C, Vermont, C L, van der Knaap, L C, Visser, E, Branger, J, Douma, R A, Cents-Bosma, A S, Duijf-van de Ven, C J H M, Schippers, E F, van Nieuwkoop, C, van Ijperen, J M, Geilings, J, van der Hut, G, van Burgel, N D, Leyten, E M S, Gelinck, L B S, Mollema, F, Davids-Veldhuis, S, Tearno, C, Wildenbeest, G S, Heikens, E, Groeneveld, P H P, Bouwhuis, J W, Lammers, A J J, Kraan, S, van Hulzen, A G W, Kruiper, M S M, van der Bliek, G L, Bor, P C J, Debast, S B, Wagenvoort, G H J, Kroon, F P, de Boer, M G J, Jolink, H, Lambregts, M M C, Roukens, A H E, Scheper, H, Dorama, W, van Holten, N, Claas, E C J, Wessels, E, den Hollander, J G, El Moussaoui, R, Pogany, K, Smit, J V, Struik-Kalkman, D, van Niekerk, T, Pontesilli, O, Lowe, S H, Oude Lashof, A M L, Posthouwer, D, van Wolfswinkel, M E, Ackens, R P, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I H M, Havenith, T R A, van Vonderen, M G A, Kampschreur, L M, Faber, S, Steeman-Bouma, R, Al Moujahid, A, Kootstra, G J, Delsing, C E, van der Burg-van de Plas, M, Scheiberlich, L, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F A, Cohen Stuart, J W T, Jansen, E R, Hoogewerf, M, Rozemeijer, W, van der Reijden, W A, Sinnige, J C, Brinkman, K, van den Berk, G E L, Blok, W L, Lettinga, K D, de Regt, M, Schouten, W E M, Stalenhoef, J E, Veenstra, J, Vrouenraets, S M E, Blaauw, H, Geerders, G F, Kleene, M J, Kok, M, Knapen, M, van der Meché, I B, Mulder-Seeleman, E, Toonen, A J M, Wijnands, S, Wttewaal, E, Kwa, D, van Crevel, R, van Aerde, K, Dofferhoff, A S M, Henriet, S S V, Ter Hofstede, H J M, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K J T, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F F, Burger, D, Gisolf, E H, Hassing, R J, Claassen, M, Ter Beest, G, van Bentum, P H M, Langebeek, N, Tiemessen, R, Swanink, C M A, van Lelyveld, S F L, Soetekouw, R, van der Prijt, L M M, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B L, Veenendaal, D, Verhagen, D W M, Lauw, F N, van Broekhuizen, M C, van Wijk, M, Bierman, W F W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Postma, D F, Schölvinck, E H, Stienstra, Y, Verhage, A R, Wouthuyzen-Bakker, M, Boonstra, A, de Groot-de Jonge, H, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Knoester, M, Hoepelman, A I M, Arends, J E, Barth, R E, Bruns, A H W, Ellerbroek, P M, Mudrikova, T, Oosterheert, J J, Schadd, E M, van Welzen, B J, Aarsman, K, Griffioen-van Santen, B M G, de Kroon, I, van Berkel, M, van Rooijen, C S A M, Schuurman, R, Verduyn-Lunel, F, Wensing, A M J, Bont, L J, Geelen, S P M, Loeffen, Y G T, Wolfs, T F W, Nauta, N, Rooijakkers, E O W, Holtsema, H, Voigt, R, van de Wetering, D, Alberto, A, van der Meer, I, Rosingh, A, Halaby, T, Zaheri, S, Boyd, A C, Bezemer, D O, van Sighem, A I, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Brétin, N, Djoechro, E, Groters, M, Kruijne, E, Lelivelt, K J, Lodewijk, C, Lucas, E, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnörr, P, Scheigrond, A, Tuijn, E, Veenenberg, L, Visser, K M, Witte, E C, Van Frankenhuijsen, Maartje, Allegre, Thierry, Makhloufi, Djamila, Livrozet, Jean-Michel, Chiarello, Pierre, Godinot, Mathieu, Brunel-Dalmas, Florence, Gibert, Sylvie, Trepo, Christian, Peyramond, Dominique, Miailhes, Patrick, Koffi, Joseph, Thoirain, Valérie, Brochier, Corinne, Baudry, Thomas, Pailhes, Sylvie, Lafeuillade, Alain, Philip, Gisèle, Hittinger, Gilles, Assi, Assi, Lambry, Véronique, Rosenthal, Eric, Naqvi, Alissa, Dunais, Brigitte, Cua, Eric, Pradier, Christian, Durant, Jacques, Joulie, Aline, Quinsat, Denis, Tempesta, Serge, Ravaux, Isabelle, Martin, Isabelle Poizot, Faucher, Olivia, Cloarec, Nicolas, Champagne, Hélène, Pichancourt, Gilles, Morlat, Philippe, Pistone, Thierry, Bonnet, Fabrice, Mercie, Patrick, Faure, Isabelle, Hessamfar, Mojgan, Malvy, Denis, Lacoste, Denis, Pertusa, Marie-Carmen, Vandenhende, Marie-Anne, Bernard, Noëlle, Paccalin, François, Martell, Cédric, Roger-Schmelz, Julien, Receveur, Marie-Catherine, Duffau, Pierre, Dondia, Denis, Ribeiro, Emmanuel, Caltado, Sabrina, Neau, Didier, Dupont, Michel, Dutronc, Hervé, Dauchy, Frédéric, Cazanave, Charles, Vareil, Marc-Olivier, Wirth, Gaétane, Le Puil, Séverine, Pellegrin, Jean-Luc, Raymond, Isabelle, Viallard, Jean-François, Chaigne de Lalande, Severin, Garipuy, Daniel, Delobel, Pierre, Obadia, Martine, Cuzin, Lise, Alvarez, Muriel, Biezunski, Noemie, Porte, Lydie, Massip, Patrice, Debard, Alexa, Balsarin, Florence, Lagarrigue, Myriam, Prevoteau du Clary, François, Aquilina, Christian, Reynes, Jacques, Baillat, Vincent, Merle, Corinne, Lemoing, Vincent, Atoui, Nadine, Makinson, Alain, Jacquet, Jean Marc, Psomas, Christina, Tramoni, Christine, Aumaitre, Hugues, Saada, Mathieu, Medus, Marie, Malet, Martine, Eden, Aurélia, Neuville, Ségolène, Ferreyra, Milagros, Sotto, Albert, Barbuat, Claudine, Rouanet, Isabelle, Leureillard, Didier, Mauboussin, Jean-Marc, Lechiche, Catherine, Donsesco, Régine, Cabie, André, Abel, Sylvie, Pierre-Francois, Sandrine, Batala, Anne-Sophie, Cerland, Christophe, Rangom, Camille, Theresine, Nadine, Hoen, Bruno, Lamaury, Isabelle, Fabre, Isabelle, Schepers, Kinda, Curlier, Elodie, Ouissa, Rachida, Gaud, Catherine, Ricaud, Carole, Rodet, Roland, Wartel, Guillaume, Sautron, Carmele, Beck-Wirth, Geneviève, Michel, Catherine, Beck, Charles, Halna, Jean-Michel, Kowalczyk, Jakub, Benomar, Meryem, Drobacheff-Thiebaut, Christine, Chirouze, Catherine, Faucher, Jean-François, Parcelier, François, Foltzer, Adeline, Haffner-Mauvais, Cécile, Hustache Mathieu, Mathieu, Proust, Aurélie, Piroth, Lionel, Chavanet, Pascal, Duong, Michel, Buisson, Marielle, Waldner, Anne, Mahy, Sophie, Gohier, Sandrine, Croisier, Delphine, May, Thierry, Delestan, Mikael, Andre, Marie, Zadeh, Mahsa Mohseni, Martinot, Martin, Rosolen, Béatrice, Pachart, Anne, Martha, Benoît, Jeunet, Noëlle, Rey, David, Cheneau, Christine, Partisani, Maria, Priester, Michèle, Bernard-Henry, Claudine, Batard, Marie-Laure, Fischer, Patricia, Berger, Jean-Luc, Kmiec, Isabelle, Robineau, Olivier, Huleux, Thomas, Ajana, Faïza, Alcaraz, Isabelle, Allienne, Christophe, Baclet, Véronique, Meybeck, Agnès, Valette, Michel, Viget, Nathalie, Aissi, Emmanuelle, Biekre, Raphael, Cornavin, Pauline, Merrien, Dominique, Seghezzi, Jean-Christophe, Machado, Moise, Diab, Georges, Raffi, François, Bonnet, Bénédicte, Allavena, Clotilde, Grossi, Olivier, Reliquet, Véronique, Billaud, Eric, Brunet, Cecile, Bouchez, Sabelline, Morineau-Le Houssine, Pascale, Sauser, Fabienne, Boutoille, David, Besnier, Michel, Hue, Hervé, Hall, Nolwenn, Brosseau, Delphine, Souala, Faouzi, Michelet, Christian, Tattevin, Pierre, Arvieux, Cédric, Revest, Matthieu, Leroy, Helene, Chapplain, Jean-Marc, Dupont, Matthieu, Fily, Fabien, Patra-Delo, Solène, Lefeuvre, Céline, Bernard, Louis, Bastides, Frédéric, Nau, Pascale, Verdon, Renaud, de la Blanchardiere, Arnaud, Martin, Anne, Feret, Philippe, Geffray, Loïk, Daniel, Corinne, Rohan, Jennifer, Fialaire, Pascale, Chennebault, Jean Marie, Rabier, Valérie, Abgueguen, Pierre, Rehaiem, Sami, Luycx, Odile, Niault, Mathilde, Moreau, Philippe, Poinsignon, Yves, Goussef, Marie, Mouton-Rioux, Virginie, Houlbert, Dominique, Alvarez-Huve, Sandrine, Barbe, Frédérique, Haret, Sophie, Perre, Philippe, Leantez-Nainville, Sophie, Esnault, Jean-Luc, Guimard, Thomas, Suaud, Isabelle, Girard, Jean-Jacques, Simonet, Véronique, Debab, Yasmine, Schmit, Jean-Luc, Jacomet, Christine, Weinberck, Pierre, Genet, Claire, Pinet, Pauline, Ducroix, Sophie, Durox, Hélène, Denes, Éric, Abraham, Bruno, Gourdon, Florence, Antoniotti, Odile, Molina, Jean-Michel, Ferret, Samuel, Lascoux-Combe, Caroline, Lafaurie, Matthieu, Colin de Verdiere, Nathalie, Ponscarme, Diane, De Castro, Nathalie, Aslan, Alexandre, Rozenbaum, Willy, Pintado, Claire, Clavel, François, Taulera, Olivier, Gatey, Caroline, Munier, Anne-Lise, Gazaigne, Sandrine, Penot, Pauline, Conort, Guillaume, Lerolle, Nathalie, Leplatois, Anne, Balausine, Stéphanie, Delgado, Jeannine, Timsit, Julie, Tabet, Magda, Gerard, Laurence, Girard, Pierre-Marie, Picard, Odile, Tredup, Jürgen, Bollens, Diane, Valin, Nadia, Campa, Pauline, Bottero, Julie, Lefebvre, Benedicte, Tourneur, Muriel, Fonquernie, Laurent, Wemmert, Charlotte, Lagneau, Jean-Luc, Yazdanpanah, Yazdan, Phung, Bao, Pinto, Adriana, Vallois, Dorothée, Cabras, Ornella, Louni, Françoise, Pialoux, Gilles, Lyavanc, Thomas, Berrebi, Valérie, Chas, Julie, Lenagat, Sophie, Rami, Agathe, Diemer, Myriam, Parrinello, Maguy, Depond, Audrey, Salmon, Dominique, Guillevin, Loïc, Tahi, Tassadit, Belarbi, Linda, Loulergue, Pierre, Zak Dit Zbar, Olivier, Launay, Odile, Silbermann, Benjamin, Leport, Catherine, Alagna, Laura, Pietri, Marie-Pierre, Simon, Anne, Bonmarchand, Manuela, Amirat, Naouel, Pichon, François, Kirstetter, Myriam, Katlama, Christine, Valantin, Marc Antoine, Tubiana, Roland, Caby, Fabienne, Schneider, Luminita, Ktorza, Nadine, Calin, Ruxandra, Merlet, Audrey, Ben Abdallah, Saadia, Weiss, Laurence, Buisson, Martin, Batisse, Dominique, Karmochine, Marina, Pavie, Juliette, Minozzi, Catherine, Jayle, Didier, Castel, Philippe, Derouineau, Jean, Kousignan, Pascale, Eliazevitch, Murielle, Pierre, Isabelle, Collias, Lio, Viard, Jean-Paul, Gilquin, Jacques, Sobel, Alain, Slama, Laurence, Ghosn, Jade, Hadacek, Blanka, Thu-Huyn, Nugyen, Nait-Ighil, Lella, Cros, Agnes, Maignan, Aline, Duvivier, Claudine, Consigny, Paul Henri, Lanternier, Fanny, Shoai-Tehrani, Michka, Touam, Fatima, Jerbi, Saadia, Bodard, Loïc, Jung, Corinne, Goujard, Cécile, Quertainmont, Yann, Duracinsky, Martin, Segeral, Olivier, Blanc, Arnaud, Peretti, Delphine, Cheret, Antoine, Chantalat, Christelle, Dulucq, Marie Josée, Levy, Yves, Lelievre, Jean Daniel, Lascaux, Anne Sophie, Dumont, Cécile, Boue, François, Chambrin, Véronique, Abgrall, Sophie, Kansau, Imad, Raho-Moussa, Mariem, De Truchis, Pierre, Dinh, Aurélien, Davido, Benjamin, Marigot, Dhiba, Berthe, Huguette, Devidas, Alain, Chevojon, Pierre, Chabrol, Amélie, Agher, Nouara, Lemercier, Yvon, Chaix, Fabrice, Turpault, Isabelle, Bouchaud, Olivier, Honore, Patricia, Rouveix, Elisabeth, Reimann, Evelyne, Belan, Alix Greder, Godin Collet, Claire, Souak, Safia, Mortier, Emmanuel, Bloch, Martine, Simonpoli, Anne-Marie, Manceron, Véronique, Cahitte, Isabelle, Hiraux, Emmanuel, Lafon, Erik, Cordonnier, François, Zeng, Ai-Feng, Zucman, David, Majerholc, Catherine, Bornarel, Dominique, Uludag, Agnès, Gellen-Dautremer, Justine, Lefort, Agnès, Bazin, Christine, Daneluzzi, Vincent, Gerbe, Juliette, Jeantils, Vincent, Coupard, Mélissa, Patey, Olivier, Bantsimba, Jonas, Delllion, Sophie, Paz, Pauline Caraux, Cazenave, Benoit, Richier, Laurent, Garrait, Valérie, Delacroix, Isabelle, Elharrar, Brigitte, Vittecoq, Daniel, Bolliot, Claudine, Lepretre, Annie, Genet, Philippe, Masse, Virginie, Perrone, Véronique, Boussard, Jean-Luc, Chardon, Patricia, Froguel, Eric, Simon, Philippe, Tassi, Sylvie, Avettand Fenoel, Véronique, Barin, Francis, Bourgeois, Christine, Cardon, Fanny, Chaix, Marie-Laure, Delfraissy, Jean François, Essat, Asma, Fischer, Hugues, Lecuroux, Camille, Petrov-Sanchez, Ventzislava, Rouzioux, Christine, Saez-Cirion, Asier, Seng, Rémonie, Kuldanek, Kristin, Mullaney, Scott, Young, Carmel, Zucchetti, Antonella, Bevan, Margaret-Ann, McKernan, Sinead, Wandolo, Emily, Richardson, Celia, Youssef, Elaney, Green, Pippa, Faulkner, Sue, Faville, Rebecca, Herman, Sandra, Care, Christine, Blackman, Helen, Bellenger, Katharine, Fairbrother, Keith, Phillips, Andrew, Babiker, Abdel, Delpech, Valerie, Fidler, S, Clarke, Mindy, Fox, Julie, Gilson, R, Goldberg, David, Hawkins, David, Johnson, Anne, Johnson, Margaret, McLean, Ken, Nastouli, Eleni, Post, Frank, Kennedy, N, Pritchard, J, Andrady, U, Rajda, N, Donnelly, C, McKernan, S, Drake, S, Gilleran, G, White, D, Ross, J, Harding, J, Faville, R, Sweeney, J, Flegg, P, Toomer, S, Wilding, H, Woodward, R, Dean, G, Richardson, C, Perry, N, Gompels, M, Jennings, L, Bansaal, D, Browing, M, Connolly, L, Stanley, B, Estreich, S, Magdy, A, O'Mahony, C, Fraser, P, Jebakumar, S P R, David, L, Mette, R, Summerfield, H, Evans, M, White, C, Robertson, R, Lean, C, Morris, S, Winter, A, Faulkner, S, Goorney, B, Howard, L, Fairley, I, Stemp, C, Short, L, Gomez, M, Young, F, Roberts, M, Green, S, Sivakumar, K, Minton, J, Siminoni, A, Calderwood, J, Greenhough, D, DeSouza, C, Muthern, Lisa, Orkin, C, Murphy, S, Truvedi, M, McLean, K, Hawkins, D, Higgs, C, Moyes, A, Antonucci, S, McCormack, S, Lynn, W, Bevan, M, Fox, J, Teague, A, Anderson, J, Mguni, S, Post, F, Campbell, L, Mazhude, C, Russell, H, Carrick, G, Ainsworth, J, Waters, A, Byrne, P, Johnson, M, Kuldanek, K, Mullaney, S, Lawlor, V, Melville, R, Sukthankar, A, Thorpe, S, Murphy, C, Wilkins, E, Ahmad, S, Green, P, Tayal, S, Ong, E, Meaden, J, Riddell, L, Loay, D, Peacock, K, Blackman, H, Harindra, V, Saeed, A M, Allen, S, Natarajan, U, Williams, O, Lacey, H, Care, C, Bowman, C, Herman, S, Devendra, S V, Wither, J, Bridgwood, A, Singh, G, Bushby, S, Kellock, D, Young, S, Rooney, G, Snart, B, Currie, J, Fitzgerald, M, Arumainayyagam, J, Chandramani, S, Rajamanoharan, S, Robinson, T, Taylor, B, Brewer, C, Mayr, Christoph, Schmidt, Wolfgang, Speidel, Andrea, Strohbach, Frank, Arastéh, Keikawus, Cordes, Christiane, Stündel, Manfred, Claus, Jörg, Baumgarten, Axel, Carganico, Andreas, Ingiliz, Patrick, Dupke, Stephan, Freiwald, Matthias, Rausch, Michael, Moll, Arend, Schleehauf, Dorothea, Hintsche, Bettina, Klausen, Gerd, Jessen, Heiko, Jessen, Arne, Köppe, Siegfried, Kreckel, Peter, Schranz, Dietmar, Fischer, Klaus, Schulbin, Hubert, Speer, Miriam, Glaunsinger, Tobias, Wicke, Thomas, Bieniek, Bernhard, Hillenbrand, Heribert, Schlote, Frank, Lauenroth-Mai, Elke, Schuler, Christoph, Schürmann, Dirk, Wesselmann, Hans, Brockmeyer, Norbert, Gehring, Peter, Schmalöer, Dirk, Hower, Martin, Spornraft-Ragaller, Petra, Häussinger, Dieter, Reuter, Stefan, Esser, Stefan, Markus, Rudolf, Kreft, Burkhard, Berzow, Dirk, Christl, Andreas, Meyer, Andreas, Plettenberg, Andreas, Stoehr, Albrecht, Graefe, Katrin, Lorenzen, Thore, Adam, Axel, Schewe, Knut, Weitner, Lutwin, Fenske, Stefan, Hansen, Stefan, Stellbrink, Hans-Jürgen, Wiemer, Dorothea, Hertling, Sandra, Schmidt, Reinhold, Arbter, Peter, Claus, Bernd, Galle, Peter, Jäger, Hans, Jä Gel-Guedes, Eva, Postel, Nils, Fröschl, Monika, Spinner, Christoph, Bogner, Johannes, Salzberger, Bernd, Schölmerich, Jürgen, Audebert, Franz, Marquardt, Ties, Schaffert, Andreas, Schnaitmann, Eiko, Trein, Andreas, Frietsch, Bernhard, Müller, Marcus, Ulmer, Albrecht, Detering-Hübner, Barbara, Kern, Peter, Schubert, Franz, Dehn, Günther, Schreiber, Maria, Güler, Cengiz, Schmidt, Daniel, Meixenberger, Karolin, Medical Microbiology & Infectious Diseases, Internal Medicine, Virology, Pediatrics, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Global Health, Infectious diseases, APH - Aging & Later Life, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, VU University medical center, Surgery, AMS - Rehabilitation & Development, APH - Quality of Care, Psychiatry, Pediatric surgery, Neurology, Public and occupational health, APH - Mental Health, Pathology, Cardiology, ACS - Heart failure & arrhythmias, Anesthesiology, IOO, Rehabilitation medicine, Obstetrics and gynaecology, General practice, Gastroenterology and hepatology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Medical oncology laboratory, Hematology, Epidemiology and Data Science, Physiology, Microbes in Health and Disease (MHD), University of Oxford, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Amsterdam UMC - Amsterdam University Medical Center, The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Johns Hopkins University (JHU), Universität Zürich [Zürich] = University of Zurich (UZH), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Institut Pasteur [Paris] (IP), This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., We thank K. Fransen and G. Vanham for help with the Belgian data, O. Ratmann for help in identifying the Dutch clusters, K. Kusejko for testing for additional VB individuals in the SHCS, B. Foley for help with genome sharing, B. Dearlove and L. Thomson for help with software, and J. Herbeck and three other reviewers for helpful suggestions., Contributors and affiliations are listed in the supplementary materials., Department of Medicine, University of Helsinki, Infektiosairauksien yksikkö, HUS Inflammation Center, and Clinicum
Subjects: Adult, Male, HIV-1/genetics, Genotype, Anti-HIV Agents, Evolution, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections/drug therapy, selection, HIV Infections, Genome, Viral, heritability, epidemic, human-immunodeficiency-virus, Evolution, Molecular, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Viral, Phylogeny, Netherlands, Multidisciplinary, Genome, model, Virulence, transmission, Molecular, setpoint viral load, reverse-transcriptase, dynamics, Viral Load, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 3121 General medicine, internal medicine and other clinical medicine, Anti-HIV Agents/therapeutic use, Mutation, HIV-1, Female, progression
Abstract: Comment in Does HIV-1 virulence matter in the ART era? Lewitus E, Rolland M. Med (N Y). 2022 Apr 8;3(4):217-219. doi: 10.1016/j.medj.2022.03.003. PMID: 35590149; International audience; We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
Published: 2022

4. Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load

Author: Zhao, Lele, Wymant, Chris, Blanquart, François, Golubchik, Tanya, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela, Hall, Matthew, Hoe Ong, Swee, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M. Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F., Kivelä, Pia, Kouyos, Roger D., Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, van Sighem, Ard, van der Valk, Marc, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Ferretti, Luca, on behalf of the BEEHIVE Collaboration, Blanquart, François, University of Oxford, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory (EMBL), Amsterdam UMC - Amsterdam University Medical Center, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Johns Hopkins University (JHU), University hospital of Zurich [Zurich], Helsinki University Hospital [Finland] (HUS), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Medical Microbiology and Infection Prevention, Infectious diseases, AII - Infectious diseases, APH - Digital Health, APH - Personalized Medicine, APH - Global Health, Global Health, APH - Aging & Later Life, University of Zurich, Ferretti, Luca, HUS Internal Medicine and Rehabilitation, Department of Medicine, University of Helsinki, and Infektiosairauksien yksikkö
Subjects: 11832 Microbiology and virology, between-host evolution, diagnosis, tansmission fitness, [SDV]Life Sciences [q-bio], 2404 Microbiology, antiretroviral therapy, 610 Medicine & health, heritability, Microbiology, initiation, 10234 Clinic for Infectious Diseases, virulence, [SDV] Life Sciences [q-bio], Virology, 2406 Virology, HIV-1, rna, ddc:610, 3111 Biomedicine, set-point viral load, 610 Medizin und Gesundheit, prognostic markers, time
Abstract: Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. Here we aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. We used the local branching index (LBI) as a proxy for transmission fitness. We found that LBI is more sensitive to differences in infectiousness than to differences in the duration of the infectious state. By analysing subtype-B samples from the Bridging the Evolution and Epidemiology of HIV in Europe project, we inferred a significant positive relationship between SPVL and LBI up to approximately 105 copies/ml, with some evidence for a peak around this value of SPVL. This is evidence of selection against low values of SPVL in HIV-1 subtype-B strains, likely related to lower infectiousness, and perhaps a peak in the transmission fitness in the expected range of SPVL. The less prominent signatures of selection against higher SPVL could be explained by an inherent limit of the method or the deployment of antiretroviral therapy.
Published: 2022

5. Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated hiv rna and dna levels as compared with therapy based on protease inhibitors

Author: Pasternak, Alexander O., Vroom, Jelmer, Kootstra, Neeltje A., Wit, Ferdinand W. N. M., de Bruin, Marijn, de Francesco, Davide, Bakker, Margreet, Sabin, Caroline A., Winston, Alan, Prins, Jan M., Reiss, Peter, Berkhout, Ben, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Experimental Immunology, APH - Aging & Later Life, Infectious diseases, and Global Health
Subjects: virus diseases
Abstract: BACKGROUND: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress HIV replication. Here, we report the results of two crosssectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). METHODS: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n=100, n=124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically-measured adherence to ART. RESULTS: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho=0.70 and rho=0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj=0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj=0.048 and padj=0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals CONCLUSIONS: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.
Published: 2021

6. Easy and accurate reconstruction of whole HIV genomes from short-read sequence data with shiver

Author: BEEHIVE Collaboration, Wymant, Chris, Blanquart, Francois, Golubchik, Tanya, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela, Croucher, Nicholas J., Hall, Matthew, Hillebregt, Mariska, Ong, Swee Hoe, Ratmann, Oliver, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Fransen, Katrien, Gourlay, Annabelle, Grabowski, M. Kate, Gunsenheimer-Bartmeyer, Barbara, Gunthard, Huldrych F., Kivelä, Pia, Kouyos, Roger, Laeyendecker, Oliver, Liitsola, Kirsi, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Cornelissen, Marion, Kellam, Paul, Reiss, Peter, Fraser, Christophe, Institute for Particle Physics Phenomenology (IPPP), Durham University, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Evolution and Ecology Research Center, University of New South Wales [Sydney] (UNSW), Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Ecole Polytechnique Fédérale de Lausanne (EPFL), University College of London [London] (UCL), Universität Zürich [Zürich] = University of Zurich (UZH), Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Department of Medicine, The Johns Hopkins University School of Medicine-Division of Infectious Diseases, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Center for Infection and Immunity Amsterdam (CINIMA), Wellcome Trust Genome Campus, Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Big Data Institute, University of Oxford, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), University of Cambridge [UK] (CAM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Johns Hopkins University (JHU), Helsinki University Hospital [Finland] (HUS), Division of Intramural Research [Bethesda, MD, USA] (Cardiovascular Branch), National Institutes of Health [Bethesda] (NIH)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, THe BEEHIVE Collaboration, European Project: 339251,EC:FP7:ERC,ERC-2013-ADG,BEEHIVE(2014), AII - Infectious diseases, Medical Microbiology, APH - Aging & Later Life, Infectious diseases, Global Health, Clinicum, Infektiosairauksien yksikkö, HUS Inflammation Center, HUS Internal Medicine and Rehabilitation, and Bill & Melinda Gates Foundation
Subjects: 0301 basic medicine, PROTEASE, Computer science, Sequence assembly, RECOMBINATION, Computational biology, Microbiology, Genome, DNA sequencing, diversity, Set (abstract data type), 03 medical and health sciences, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:610, mapping, TYPE-1, ComputingMilieux_MISCELLANEOUS, Sequence (medicine), Contig, IDENTIFICATION, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], BEEHIVE Collaboration, HIV, INSERTIONS, food and beverages, bioinformatics, TRANSFORM, GENE, Resources, 3. Good health, Identification (information), ALIGNMENT, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, HUMAN-IMMUNODEFICIENCY-VIRUS, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, genome assembly, next-generation sequencing, 3111 Biomedicine, 610 Medizin und Gesundheit, INHIBITORS, Reference genome
Abstract: International audience; Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large betweenand within-host diversity, including frequent indels, may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to pre-process reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with the user’s choice of existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We used shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read whole-genome data produced with the Illumina platform, for sixty-five existing publicly available samples and fifty new samples. We show the systematic superiority of mapping to shiver’s constructed reference compared with mapping the same reads to the closest of 3,249 real references: median values of 13 bases called differently and more accurately, 0 bases called differently and less accurately, and 205 bases of missing sequence recovered. We also successfully applied shiver to whole-genome samples of Hepatitis C Virus and Respiratory Syncytial Virus. shiver is publicly available from https://github.com/ChrisHIV/shiver.
Published: 2018

7. Workup of Human Blood Samples for Deep Sequencing of HIV-1 Genomes

Author: Cornelissen, Marion, Gall, Astrid, van der Kuyl, Antoinette, Wymant, Chris, Blanquart, François, Fraser, Christophe, Berkhout, Ben, AII - Infectious diseases, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity
Abstract: We describe a detailed protocol for the manual workup of blood (plasma/serum) samples from individuals infected with the human immunodeficiency virus type 1 (HIV-1) for deep sequence analysis of the viral genome. The study optimizing the assay was performed in the context of the BEEHIVE (Bridging the Evolution and Epidemiology of HIV in Europe) project, which analyzes complete viral genomes from more than 3000 HIV-1-infected Europeans with high-throughput deep sequencing techniques. The goal of the BEEHIVE project is to determine the contribution of viral genetics to virulence. Recently we performed a pilot experiment with 125 patient plasma samples to identify the method that is most suitable for isolation of HIV-1 viral RNA for subsequent long-amplicon deep sequencing. We reported that manual isolation with the QIAamp Viral RNA Mini Kit (Qiagen) provides superior results over robotically extracted RNA. The latter approach used the MagNA Pure 96 System in combination with the MagNA Pure 96 Instrument (Roche Diagnostics), the QIAcube robotic system (Qiagen), or the mSample Preparation Systems RNA kit with automated extraction by the m2000sp system (Abbott Molecular). Here we present a detailed protocol for the labor-intensive manual extraction method that yielded the best results
Published: 2018

8. Foreword

Author: Beerenwinkel, Niko, Berkhout, Ben, Domingo, Esteban, AII - Infectious diseases, Medical Microbiology, and Amsterdam institute for Infection and Immunity
Published: 2017

9. RNAi and Cellular miRNAs in Infections by Mammalian Viruses

Author: Haasnoot, Joost, Berkhout, Ben, Other departments, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Subjects: Mammals, microRNA, viruses, Article, Virus, MicroRNAs, RNA interference, HCV, Host-Pathogen Interactions, Viruses, HIV-1, Adenovirus, Animals, Humans, RNA silencing suppressor, RNA, Small Interfering, Regulation, Virus Physiological Phenomena
Abstract: MicroRNAs (miRNAs) play an essential role in the regulation of eukaryotic gene expression. Recent studies demonstrate that miRNAs can also strongly affect the replication of pathogenic viruses. For example, cellular miRNAs can target and repress the expression of viral mRNAs, but there is also at least one example of a cellular miRNA that stimulates virus replication. Furthermore, viruses can encode their own miRNAs, trigger changes in cellular miRNA expression or encode RNA silencing suppressor factors that inhibit cellular miRNAs. These interactions together form a complex regulatory network that controls both viral and host gene expression, which ultimately determines the outcome of viral infection at the cellular level and disease progression in the host. Here, we summarize the literature data on such virus-cell interactions in mammals and discuss how miRNAs can be used as research tools or targets in the development of novel antiviral therapeutics.
Published: 2010

10. HIV infection and adipose tissue resident stem cells: their involvement in pathology and treatment

Author: Roy, Upal, Berkhout, Ben, Hayat, M. A., Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2015

11. Gene Therapy Strategies to Block HIV-1 Replication by RNA Interference

Author: Herrera-Carrillo, Elena, Berkhout, Ben, Medical Microbiology and Infection Prevention, and AII - Amsterdam institute for Infection and Immunity
Abstract: The cellular mechanism of RNA interference (RNAi) plays an antiviral role in many organisms and can be used for the development of therapeutic strategies against viral pathogens. Persistent infections like the one caused by the human immunodeficiency virus type 1 (HIV-1) likely require a durable gene therapy approach. The continuous expression of the inhibitory RNA molecules in T cells is needed to effectively block HIV-1 replication. We discuss here several issues, ranging from the choice of RNAi inhibitor and vector system, finding the best target in the HIV-1 RNA genome, alternatively by targeting host mRNAs that encode important viral cofactors, to the setup of appropriate preclinical test systems. Finally, we briefly discuss the relevance of this topic for other viral pathogens that cause a chronic infection in humans
Published: 2015

12. Gene Therapy for HIV and Chronic Infections Preface

Author: Berkhout, Ben, Ertl, Hildegund C. J., Weinberg, Marc S., Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2015

13. Hiv-1-transcriptie: recente verrassingen

Author: Harwig, Alex, Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2015

14. Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

Author: van Montfort, Thijs, Thomas, Adri A M, Krawczyk, Przemek M, Berkhout, Ben, Sanders, Rogier W, Paxton, William A, Sub Developmental Biology, Dep Biologie, Developmental Biology, Sub Developmental Biology, Dep Biologie, Developmental Biology, Medical Microbiology and Infection Prevention, Cancer Center Amsterdam, Cell Biology and Histology, and Amsterdam institute for Infection and Immunity
Subjects: chemistry.chemical_classification, biology, Immunology, virus diseases, Dendritic Cells, HIV Antibodies, HIV Envelope Protein gp120, V3 loop, Gp41, Antibodies, Neutralizing, Virology, Neutralization, Epitope, Cell Line, Epitopes, chemistry, Cell culture, HIV-1, biology.protein, Humans, Immunology and Allergy, Virus Activation, Antibody, Binding site, Glycoprotein
Abstract: Ab-neutralized HIV-1 can be captured by dendritic cells (DCs), which subsequently transfer infectious HIV-1 to susceptible CD4+ T cells. In this study, we examined the capacity of early Abs, as well as recently identified broadly neutralizing Abs (bNAbs) targeting different envelope glycoprotein (Env) epitopes, to block HIV-1 transmission by immature and mature DCs to HIV-1–sensitive cells. Three bNAbs directed against the gp41 membrane proximal region of Env (2F5, 4E10, and 10E8) and three gp120 bNAbs targeting the CD4 binding site (b12, VRC01, and NIH45-46) were examined. In addition, eight glycan-dependent bNAbs targeting the V1V2 apex (PG9, PG16, and PGT145), the V3 loop (2G12, PGT121, and PGT128), and the gp120–gp41 interface of Env (PGT151 and 35O22) were tested. bNAbs that bound specific glycans showed, depending on the immature or mature state of the DC, diverse efficiencies in HIV-1 trans-infection. All bNAbs that bound the CD4 binding site blocked trans-infection, whereas all bNAbs directed against the membrane proximal region lost neutralizing activity after DC-mediated HIV-1 transmission. To understand how preneutralized HIV-1 can be transferred as infectious virus by DCs, we followed the processing of 2F5-treated HIV-1 by DCs with confocal microscopy. Inhibition of DC-internalization pathways could not reverse the dissociation of 2F5 from HIV-1, suggesting that Ab dissociation occurs directly at the plasma membrane. Collectively, these findings imply that the location of the epitope and the neutralization capacity of these Abs determine the efficiency of DC-mediated HIV-1 transfer.
Published: 2015

15. Interaction between the spike protein of human coronavirus NL63 and its cellular receptor ACE2

Author: Pöhlmann, Stefan, Gramberg, Thomas, Wegele, Anja, Pyrc, Krzysztof, van der Hoek, Lia, Berkhout, Ben, Hofmann, Heike, Perlman, S., Holmes, K. V., AII - Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Subjects: Human coronavirus NL63, chemistry.chemical_classification, biology, viruses, Protein subunit, virus diseases, Lipid bilayer fusion, Plasma protein binding, medicine.disease_cause, biology.organism_classification, Virology, chemistry, Viral envelope, medicine, Glycoprotein, Receptor, Coronavirus
Abstract: Coronavirus (CoV) infection of humans has so far not been associated with severe disease. However, the discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (hCoVs) can evolve. As the characterization of new hCoVs is therefore an important task, we studied the cellular entry of hCoV-NL63, which was recently isolated from patients with lower respiratory tract illness. Entry of CoVs into target cells is determined by the major viral envelope glycoprotein termed “spike” (S), which provides the virions with their characteristic corona-like shape. The main function of the S-protein in CoV entry is the binding to a host cell receptor followed by fusion of viral and cellular membranes. The domains in S that are required for membrane fusion locate to the C-terminal half of the protein (S2 subunit). Receptor engagement is conferred by the N-terminal S1 subunit; consequently, 6
Published: 2006

16. A novel approach for inhibition of HIV-1 by RNA interference: counteracting viral escape with a second generation of siRNAs

Author: ter Brake, Olivier, Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Subjects: combinatorial therapy, RNA interference, shRNA, siRNA, lentiviral vector, HIV-1, Review Article, gene therapy
Abstract: RNA interference (RNAi) is an evolutionary conserved gene silencing mechanism in which small interfering RNA (siRNA) mediates the sequence specific degradation of mRNA. The recent discovery that exogenously delivered siRNA can trigger RNAi in mammalian cells raises the possibility to use this technology as a therapeutic tool against pathogenic viruses. Indeed, it has been shown that siRNAs can be used effectively to inhibit virus replication. The focus of this review is on RNA interference strategies against HIV-1 and how this new technology may be developed into a new successful therapy. One of the hallmarks of RNAi, its sequence specificity, also presents a way out for the virus, as single nucleotide substitutions in the target region can abolish the suppression. Strategies to prevent the emergence of resistant viruses have been suggested and involve the targeting of conserved sequences and the simultaneous use of multiple siRNAs, similar to current highly active antiretroviral therapy. We present an additional strategy aimed at preventing viral escape by using a second generation of siRNAs that recognize the mutated target sites.
Published: 2005

17. SPECIAL ISSUE: Retroviral Nucleocapsid Protein and Assembly Foreword

Author: Berkhout, Ben, Mouland, Andrew J., Musier-Forsyth, Karin, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2014

18. HIV-1-based lentiviral vectors

Author: Liu, Ying Poi, Berkhout, Ben, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity
Abstract: Numerous viral vectors have been developed for the delivery of transgenes to specific target cells. For persistent transgene expression, vectors based on retroviruses are attractive delivery vehicles because of their ability to stably integrate their DNA into the host cell genome. Initially, vectors based on simple retroviruses were the vector of choice for such applications. However, these vectors can only transduce actively dividing cells. Therefore, much interest has turned to retroviral vectors based on the lentivirus genus because of their ability to transduce both dividing and non-dividing cells. The best characterized lentiviral vectors are derived from the human immunodeficiency virus type 1 (HIV-1). This chapter describes the basic features of the HIV-1 replication cycle and the many improvements reported for the lentiviral vector systems to increase the safety and efficiency. We also provide practical information on the production of HIV-1 derived lentiviral vectors, the cell transduction protocol and a method to determine the transduction titers of a lentiviral vector
Published: 2014

19. Gene Silencing Methods Using Vector-Encoded siRNAs or miRNAs

Author: Liu, Ying Poi, Berkhout, Ben, Hartmann, Roland K., Bindereif, Albrecht, Schön, Astrid, Westhof, Eric, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity
Subjects: Small hairpin RNA, Transduction (genetics), Small interfering RNA, RNA interference, microRNA, Trans-acting siRNA, Gene silencing, Computational biology, Biology, Molecular biology, Viral vector
Published: 2014

20. Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Author: Gras, Luuk, Geskus, Ronald B., Jurriaans, Suzanne, Bakker, Margreet, van Sighem, Ard, Bezemer, Daniela, Fraser, Christophe, Prins, Jan M., Berkhout, Ben, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Boer, K., van der Meer, J. T.M., Wit, F. W.M.N., Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J.B., Lange, J. M.A., Geerlings, S. E., van Vugt, M., Vrouenraets, S. M.E., Pajkrt, D., Bos, J. C., van der Valk, M., Schreij, G., Lowe, S., Oude Lashof, A., Pronk, M. J.H., Bravenboer, B., van der Ende, M. E., de Vries-Sluijs, T. E.M.S., Schurink, C. A.M., van der Feltz, M., Nouwen, J. L., Gelinck, L. B.S., Verbon, A., Rijnders, B. J.A., van de Ven-de Ruiter, E. D., Slobbe, L., Kauffmann, R. H., Schippers, E. F., Groeneveld, P. H.P., Alleman, M. A., Bouwhuis, J. W., ten Kate, R. W., Soetekouw, R., Kroon, F. P., van den Broek, P. J., van Dissel, J. T., Arend, S. M., van Nieuwkoop, C., de Boer, M. G.J., Jolink, H., den Hollander, J. G., Pogany, K., Bronsveld, W., Kortmann, W., van Twillert, G., van Houte, D. P.F., Polée, M. B., van Vonderen, M. G.A., ten Napel, C. H.H., Kootstra, G. J., Brinkman, K., Blok, W. L., Frissen, P. H.J., Schouten, W. E.M., van den Berk, G. E.L., Juttmann, J. R., van Kasteren, M. E.E., Brouwer, A. E., Mulder, J. W., van Gorp, E. C.M., Smit, P. M., Weijer, S., van Eeden, A., Verhagen, D. W.M., Sprenger, H. G., Doedens, R., Scholvinck, E. H., van Assen, S., Stek, C. J., Hoepelman, I. M., Mudrikova, T., Schneider, M. M.E., Jaspers, C. A.J.J., Ellerbroek, P. M., Peters, E. J.G., Maarschalk-Ellerbroek, L. J., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W.M., van der Hilst, J. C.H., Richter, C., van der Berg, J. P., Gisolf, E. H., Internal medicine, Pediatric surgery, Plastic, Reconstructive and Hand Surgery, CCA - Innovative therapy, Pathology, Graduate School, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Epidemiology and Data Science, Medical Microbiology and Infection Prevention, Infectious diseases, Other departments, Paediatric Infectious Diseases / Rheumatology / Immunology, Other Research, Obstetrics and Gynaecology, Global Health, General Internal Medicine, Center of Experimental and Molecular Medicine, Medische Microbiologie, Interne Geneeskunde, and RS: CAPHRI School for Public Health and Primary Care
Subjects: analytical parameters, Epidemiology, lcsh:Medicine, Human immunodeficiency virus 1, men who have sex with men, HIV Infections, epidemic, Men who have sex with men, Efficacy, Immunodeficiency Viruses, Antiretroviral Therapy, Highly Active, antiviral therapy, Natural Selection, Non-U.S. Gov't, lcsh:Science, Epidemiological Methods, Netherlands, Multidisciplinary, antiretrovirus agent, Research Support, Non-U.S. Gov't, adult, disease course, article, Homosexuality, HIV epidemiology, Censoring (clinical trials), Medicine, Infectious diseases, Viral load, Research Article, Evolutionary Processes, Retrovirology and HIV immunopathogenesis, Antiretroviral Therapy, Viral diseases, Research Support, Microbiology, Viral Evolution, virus RNA, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, male, Human immunodeficiency virus infection, Virology, medicine, Journal Article, Humans, Highly Active, human, Homosexuality, Male, Seroconversion, Biology, seroconversion, Evolutionary Biology, Surrogate endpoint, business.industry, human cell, lcsh:R, HIV, CD4 lymphocyte count, medicine.disease, Antiretroviral therapy, major clinical study, drug efficacy, adolescent, Immunology, lcsh:Q, business, Demography
Abstract: Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, 3, or AIDS) among therapy-naïve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process.Results:All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm3 for 1984-1995 [n = 111], 1996-2002 [n = 139], and 2003-2007 seroconverters [n = 356], respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm3 for 1984-1995 seroconverters and 308 cells/mm3 for 2003-2007 seroconverters (difference in slope, p = 0.045).Conclusion:Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996.
Published: 2013

21. Kuan-Teh Jeang Obituary

Author: Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2013

22. Design of lentivirally expressed siRNAs

Author: Liu, Ying Poi, Berkhout, Ben, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity
Subjects: fungi
Abstract: RNA interference (RNAi) has been widely used as a tool for gene knockdown in fundamental research and for the development of new RNA-based therapeutics. The RNAi pathway is typically induced by expression of ∼22 base pair (bp) small interfering RNAs (siRNAs), which can be transfected into cells. For long-term gene silencing, short hairpin RNA (shRNA), or artificial microRNA (amiRNA) expression constructs have been developed that produce these RNAi inducers inside the cell. Currently, these types of constructs are broadly applied to knock down any gene of interest. Besides mono RNAi strategies that involve single shRNAs or amiRNAs, combinatorial RNAi approaches have been developed that allow the simultaneous expression of multiple siRNAs or amiRNAs by using polycistrons, extended shRNAs (e-shRNAs), or long hairpin RNAs (lhRNAs). Here, we provide practical information for the construction of single shRNA or amiRNA vectors, but also multi-shRNA/amiRNA constructs. Furthermore, we summarize the advantages and limitations of the most commonly used viral vectors for the expression of RNAi inducers
Published: 2013

23. Droplet digital PCR, the new tool in HIV reservoir quantification?

Author: De Spiegelaere, Ward, Kiselinova, Maja, Malatinková, Eva, Pasternak, Alexander, Berkhout, Ben, and Vandekerckhove, Linos
Subjects: reservoir, digital PCR, Biology and Life Sciences, ddPCR, HIV, HIV latency, quantification
Abstract: Background: Digital PCR is a relatively old concept for absolute quantification of DNA using PCR, but recent technological developments allowed its wide use. The current state of art technique for performing digital PCR is based on microdroplet technology. Direct absolute quantification relieves the necessity of standard curves and increases assay accuracy. In addition, the end point PCR set-up allows higher assay flexibility and decreases quantitative bias due to variations in PCR efficiency. In the present work, these theoretical advantages were assessed on the QX100 droplet digital PCR (Bio-rad) on various virological markers to assess the possible use of ddPCR in HIV research. Methods: First, ddPCR was compared to a highly sensitive method of real-time PCR based quantification of cellular associated spliced and unspliced HIV RNA. Second, different methods of DNA extractions in combination with ddPCR were compared for quantification of total and episomal HIV DNA. Hereby, the maximal amount of restriction digested DNA was assessed in the ddPCR. Third, a touchdown procedure was optimized for an HIV specific primer probe set with a low melting temperature using touchdown ddPCR. Results: The comparsion of the nested real-time quantitative PCR to ddPCR indicated that ddPCR is at least equally sensitive to qPCR but also that false positive negative control samples may interfere with quantification at the level of single copies. Episomal 2LTR quantification was compared on ddPCR between total DNA extracted DNA and plasmid purified DNA, revealing a higher accuracy of 2LTR measurements in the total DNA extracts. Assessment of total DNA load in digital PCR reactions revealed a higher tolerance for inhibition compared to qPCR, but a strong influence of the concentration of restriction digestion mix on ddPCR efficiency. Finally, a touchdown procedure revealed that digital PCR can combine a higher flexibility in assay design while retaining accurate quantitative power compared to qPCR Conclusions: We transferred 4 assays used in HIV reservoir research to the ddPCR platform. Although ddPCR has some major advantages for low level quantification in HIV reservoir research, some technical hurdles, including the occurrence of false negative control samples need still be addressed to ameliorate the current technology.
Published: 2013

24. Towards an HIV cure: a global scientific strategy

Author: International AIDS Society Scientific Working Group on HIV Cure, Deeks, Steven G, Autran, Brigitte, Berkhout, Ben, Benkirane, Monsef, Cairns, Scott, Chomont, Nicolas, Chun, Tae-Wook, Churchill, Melissa, Di Mascio, Michele, Katlama, Christine, Lafeuillade, Alain, Landay, Alan, Lederman, Michael, Lewin, Sharon R, Maldarelli, Frank, Margolis, David, Markowitz, Martin, Martinez-Picado, Javier, Mullins, James I, Mellors, John, Moreno, Santiago, O'Doherty, Una, Palmer, Sarah, Penicaud, Marie-Capucine, Peterlin, Matija, Poli, Guido, Routy, Jean-Pierre, Rouzioux, Christine, Silvestri, Guido, Stevenson, Mario, Telenti, Amalio, Van Lint, Carine, Verdin, Eric, Woolfrey, Ann, Zaia, John, and Barré-Sinoussi, Françoise
Subjects: Prevention, Immunology, HIV, Antiretroviral Therapy, Evaluation of treatments and therapeutic interventions, HIV Infections, Virus Replication, Virus Latency, Vaccine Related, Infectious Diseases, Good Health and Well Being, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Humans, HIV/AIDS, Highly Active, Immunization, Development of treatments and therapeutic interventions, International AIDS Society Scientific Working Group on HIV Cure, Vaccine Related (AIDS), Infection
Abstract: Given the limitations of antiretroviral therapy and recent advances in our understanding of HIV persistence during effective treatment, there is a growing recognition that a cure for HIV infection is both needed and feasible. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. Several priorities for basic, translational and clinical research were identified. This Opinion article summarizes the group's recommended key goals for the international community.
Published: 2012

25. HIV/AIDS: the possibilities of an RNAi-based gene therapy

Author: Berkhout, Ben, Bandivdekar, A. H., Puri, C. P., Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2011

26. Toward a durable treatment of HIV-1 infection using

Author: Eekels, Julia J. M., Berkhout, Ben, Grimm, Dirk, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity
Published: 2011

27. Evolution of Live-Attenuated HIV Vaccines

Author: Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Subjects: viruses
Abstract: Despite intensive research since the viral pathogen was discovered some 25 years ago, not much progress has been reported on the development of a safe vaccine that protects against human immunodeficiency virus type 1. A vaccine approach that has been abandoned because its safety cannot be guaranteed is the single vaccine candidate that provides good protection in the macaque model, a live-attenuated variant of the simian immunodeficiency virus. The attenuated virus will cause a low-grade, but persistent infection that allows optimization of viral replication kinetics over time by spontaneous virus evolution, which may increase viral pathogenicity. In this article, we discuss innovative strategies to overcome this hurdle, including the generation of "single-cycle" viruses and a conditionally replicating HIV-1 variant
Published: 2011

28. Recent Advances in Human Retroviruses: Principles of Replication and Pathogenesis

Author: Lever, Andrew M. L., Jeang, Kuan-Teh, Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2010

29. Natuurlijke resistentie tegen het humaan immunodeficiëntie virus (HIV)

Author: Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2010

30. Lentiviral Vector Engineering for Anti-HIV RNAi Gene Therapy

Author: ter Brake, Olivier, Westerink, Jan-Tinus, Berkhout, Ben, Other departments, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Abstract: RNA interference or RNAi-based gene therapy for the treatment of HIV-1 infection has recently emerged as a highly effective antiviral approach. The lentiviral vector system is a good candidate for the expression of antiviral short hairpin RNAs (shRNA) in HIV-susceptible cells. However, this strategy can give rise to vector problems because the anti-HIV shRNAs can also target the HIV-based lentiviral vector system. In addition, there may be self-targeting of the shRNA-encoding sequences within the vector RNA genome in the producer cell. The insertion of microRNA (miRNA) cassettes in the vector may introduce Drosha cleavage sites that will also result in the destruction of the vector genome during the production and/or the transduction process. Here, we describe possible solutions to these lentiviral-RNAi problems. We also describe a strategy for multiple shRNA expression to establish a combinatorial RNAi therapy
Published: 2010

31. Sealing the Envelope - The HIV-1 Envelope Glycoproteins as Targets for Therapeutics and Vaccines

Author: Sanders, Rogier W., Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Subjects: viruses, virus diseases
Abstract: HIV-1 is an enveloped virus that derives its lipid envelope from the virus producing cell. The envelope glycoprotein complex (Env) mediates viral attachment to and entry in susceptible target cells and is therefore an attractive target for therapeutic intervention. The T20 peptide (Fuzeon, enfuvirtide), targeting the Env fusion machinery, was approved for clinical use in 2003 and served as salvage therapy for many HIV-1 infected individuals for whom no other effective inhibitors were available because of the development of viral resistance. The approval in 2007 of the small molecule inhibitor maraviroc (Selzentry, Celsentri), targeting the coreceptor CCR5, marked a new era for entry inhibitors, which now occupy a mature position in the repertoire of antiviral drugs available to clinicians
Published: 2010

32. RNAi treatment of HIV-1 infection

Author: Von Eije, Karin J., Berkhout, Ben, Erdmann, V. A., Barciszewski, Jan, Medical Microbiology, and Amsterdam institute for Infection and Immunity
Published: 2010

33. RNAi Gene Therapy to Control HIV-1 Infection

Author: Berkhout, Ben, ter Brake, Olivier, Martínez, Miguel Angel, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2010

34. HIV-1 Interactions with Small RNA Induced Silencing Mechanisms

Author: Haasnoot, Joost, Berkhout, Ben, Lever, Andrew M. L., Jeang, Kuan-Teh, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2010

35. Virus-encoded Suppressors of RNA Silencing and the Role of Cellular miRNAs in Mammalian Antiviral Immune Responses

Author: Haasnoot, Joost, Berkhout, Ben, Martínez, Miguel Angel, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2010

36. RNA Technologies and Their Applications: Chapter: RNAi Treatment of HIV-1 Infection

Author: von Eije, Karin J. and Berkhout, Ben
Published: 2010

37. Hiv-onderzoek na 25 jaar

Author: Berkhout, Ben, Schadé, A., Boenink, Annette D., Danner, S. A., Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2010

38. Nucleic acids-based therapeutics in the battle against pathogenic viruses

Author: Haasnoot, Joost, Berkhout, Ben, Medical Microbiology and Infection Prevention, and AII - Amsterdam institute for Infection and Immunity
Abstract: For almost three decades, researchers have studied the possibility to use nucleic acids as antiviral therapeutics. In theory, compounds such as antisense oligonucleotides, ribozymes, DNAzymes, and aptamers can be designed to trigger the sequence-specific inhibition of particular mRNA transcripts, including viral genomes. However, difficulties with their efficiency, off-target effects, toxicity, delivery, and stability halted the development of nucleic acid-based therapeutics that can be used in the clinic. So far, only a single antisense drug, Vitravene for the treatment of CMV-induced retinitis in AIDS patients, has made it to the clinic. Since the discovery of RNA interference (RNAi), there is a renewed interest in the development of nucleic acid-based therapeutics. Antiviral RNAi approaches are highly effective in vitro and in animal models and are currently being tested in clinical trials. Here we give an overview of antiviral nucleic acid-based therapeutics. We focus on antisense and RNAi-based compounds that have been shown to be effective in animal model systems
Published: 2009

39. Virus Evolution as a Tool to Study HIV-1 Biology

Author: Berkhout, Ben, Das, Atze T., Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Abstract: Mutational analysis of the viral genome is frequently used to study the role of sequence or structural elements in HIV-1 replication. Many laboratories that use this approach have occasionally come across revertant viruses that overcome an introduced defect either by restoration of the original sequence or by the introduction of additional mutations in the viral genome. Similarly, replication of a wild type virus under selective pressure, due to the presence of inhibitors or due to specific culture settings, may result in the appearance of evolved variants that replicate more efficiently under the applied conditions. We have developed in vitro HIV-1 evolution from an anecdotal event to a systematic research tool to study different aspects of the viral replication cycle. In this manuscript, we will briefly review the method of forced virus evolution to study HIV-1 biology and provide several examples that illustrate the power of this method, as it frequently yielded interesting and unexpected information about the mechanism of virus replication
Published: 2009

40. Towards an RNAi-based Gene Therapy

Author: Berkhout, Ben, ter Brake, Olivier, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2009

41. Detailed mechanistic insights into HIV-1 sensitivity to three generations of fusion inhibitors

Author: Eggink, Dirk, Langedijk, Johannes P.M., Bonvin, Alexandre M.J.J., Deng, Yiqun, Lu, Min, Berkhout, Ben, Sanders, Rogier W., Sub NMR Spectroscopy, NMR Spectroscopy, Medical Microbiology and Infection Prevention, Amsterdam institute for Infection and Immunity, Sub NMR Spectroscopy, and NMR Spectroscopy
Subjects: Models, Molecular, Enfuvirtide, enfuvirtide, Human immunodeficiency virus 1, Peptide, Peptide binding, Drug resistance, IC50, Biochemistry, Protein Structure, Secondary, stereospecificity, HIV Fusion Inhibitors, biophysics, electricity, Peptide sequence, chemistry.chemical_classification, article, HIV Envelope Protein gp41, unclassified drug, priority journal, Protein Structure and Folding, antiviral activity, t 2635, drug potency, medicine.drug, amino acid substitution, mutational analysis, antiviral susceptibility, drug design, tifuvirtide, Molecular Sequence Data, Static Electricity, Biology, Human immunodeficiency virus fusion inhibitor, Inhibitory Concentration 50, Viral entry, antiviral resistance, Cell Line, Tumor, medicine, physical chemistry, Humans, controlled study, Amino Acid Sequence, human, Molecular Biology, Binding Sites, human cell, Cell Biology, Fusion protein, Peptide Fragments, Protein Structure, Tertiary, circular dichroism, Heptad repeat, chemistry, Mutation, molecular interaction, HIV-1, Peptides, virus cell interaction
Abstract: Peptides based on the second heptad repeat (HR2) of viral class I fusion proteins are effective inhibitors of virus entry. One such fusion inhibitor has been approved for treatment of human immunodeficiency virus-1 (T20, enfuvirtide). Resistance to T20 usually maps to the peptide binding site in HR1. To better understand fusion inhibitor potency and resistance, we combined virological, computational, and biophysical experiments with comprehensive mutational analyses and tested resistance to T20 and second and third generation inhibitors (T1249 and T2635). We found that most amino acid substitutions caused resistance to the first generation peptide T20. Only charged amino acids caused resistance to T1249, and none caused resistance to T2635. Depending on the drug, we can distinguish four mechanisms of drug resistance: reduced contact, steric obstruction, electrostatic repulsion, and electrostatic attraction. Implications for the design of novel antiviral peptide inhibitors are discussed. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Published: 2009

42. Combinatorial RNAi strategies against HIV-1 and other escape-prone viruses

Author: Liu, Ying Poi, Berkhout, Ben, Medical Microbiology, and Amsterdam institute for Infection and Immunity
Subjects: fungi
Abstract: RNA interference (RNAi) is an evolutionarily conserved mechanism in which double-stranded RNA (dsRNA) induces sequence-specific gene silencing. RNAi as a gene suppression tool holds great promise for basic research and multiple applications. RNAi strategies with a single inhibitor have received much attention and some are currently being tested in clinical trials as potential drug for infectious diseases, cancer and genetic disorders. Although very successful, such an RNAi mono-therapy is not always sufficient. For example, several proteins should be silenced simultaneously for the elucidation of cross-talk between signalling pathways. Furthermore, development of a durable RNAi therapy for viral infections and cancer may also require the use of multiple inhibitors, as this may prevent the selection of virus variants or cancer cells that escape from the RNAi therapy by mutation of the target gene. Therefore, several combinatorial RNAi strategies have been developed and recent reports demonstrated the potency of this approach by targeting multiple viral genes or oncogenes. At the same time, combinatorial RNAi may also increase the risk of saturation of the endogenous RNAi pathway and off-target effects. This review summarizes the latest experimental advances in combinatorial RNAi research and gene therapy approaches, in particular against escape-prone viruses, like the human immunodeficiency virus type 1 (HIV-1).
Published: 2008
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43. Retroviral reverse transcription - Preface

Author: Menéndez-Arias, Luis, Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2008

44. Infectious Diseases of the Nervous System: Pathogenesis and Worldwide Impact

Author: Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2008

45. Third European Congress of Virology. 1-5 September 2007, Nuremberg, Germany

Author: Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2007

46. HIV-1 reverse transcription: close encounters between the viral genome and a cellular tRNA

Author: Abbink, Truus E. M., Berkhout, Ben, Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2007

47. HIV-1 Reverse Transcription: Close Encounters Between the Viral Genome and a Cellular tRNA

Author: Abbink, Truus E.M., Berkhout, Ben, Jeang, Kuan Teh, Pediatric surgery, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, and Jeang, Kuan Teh
Subjects: Genetics, chemistry.chemical_classification, 0303 health sciences, viruses, 030302 biochemistry & molecular biology, Human immunodeficiency virus (HIV), RNA, Biology, medicine.disease_cause, Genome, Reverse transcriptase, 3. Good health, 03 medical and health sciences, Enzyme, Viral life cycle, chemistry, Transfer RNA, medicine, Primer (molecular biology), 030304 developmental biology
Abstract: Publisher Summary This chapter focuses on the initiation step of reverse transcription as performed by human immunodeficiency virus type 1 (HIV‐1). During this step, a cellular tRNA primer is placed onto a complementary sequence in the viral genome, called the “primer‐binding site” (PBS). In this highly organized process, the cellular tRNALys3 molecule acts as primer. Retroviruses differ from other positive‐stranded RNA viruses in the process of reverse transcription. This process is an essential step in the viral life cycle as it converts the retroviral genomic RNA into a proviral DNA in a complex, multistep process. The viral enzyme reverse transcriptase (RT) recognizes the RNA–RNA complex and catalyzes the extension of the 3’ end of the tRNA primer, with the viral RNA (vRNA) acting as template. This initiation step is regulated and most retroviruses are restricted to the use of the cognate, self‐tRNA primer. Recent insight into additional contacts between the tRNA and the vRNA genome lead to a renewed attempt to change HIV‐1 primer speciﬁcity. The chapter discusses a study in which a replicating HIV‐1 variant is obtained that uses a nonself tRNA primer. The analysis of this variant confirms the role of multiple determinants of tRNA primer usage.
Published: 2007

48. Inhibition of human coronavirus NL63 infection at early stages of the replication cycle

Author: Pyrc, Krzysztof, Bosch, Berend Jan, Berkhout, Ben, Jebbink, Maarten F, Dijkman, Ronald, Rottier, Peter, van der Hoek, Lia, LS Virologie, Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, and LS Virologie
Subjects: Human coronavirus NL63, Azauridine, Time Factors, Cell Survival, Coronacrisis-Taverne, Cytidine, medicine.disease_cause, Small Interfering, Virus Replication, Antiviral Agents, Virus, Cell Line, Inhibitory Concentration 50, Cytopathogenic Effect, Viral, stomatognathic system, Nidovirales, Neutralization Tests, Receptors, medicine, Coronaviridae, Animals, Humans, Pharmacology (medical), Viral, RNA, Small Interfering, Receptor, Coronavirus, Pharmacology, biology, Base Sequence, Molecular Structure, virus diseases, Nucleosides, biology.organism_classification, Virology, Macaca mulatta, Heptad repeat, Infectious Diseases, Viral replication, RNA, RNA, Viral, Receptors, Virus, RNA Interference, Coronavirus Infections, Cytopathogenic Effect
Abstract: Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, β- d -N 4 -hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 μg/ml, 2 μM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 μM, >200 nM, >200 nM, >100 μM, and 80 μM, respectively). These agents may be investigated further for the treatment of coronavirus infections.
Published: 2006

49. Human coronavirus NL63 infection is associated with croup

Author: van der Hoek, Lia, Sure, Klaus, Ihorst, Gabriele, Stang, Alexander, Pyrc, Krzysztof, Jebbink, Maarten F., Petersen, Gudula, Forster, Johannes, Berkhout, Ben, Uberla, Klaus, AII - Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention
Published: 2006

50. Attachment factor and receptor engagement of SARS coronavirus and human coronavirus NL63

Author: Hofmann, Heike, Marzi, Andrea, Gramberg, Thomas, Geier, Martina, Pyrc, Krzysztof, Hoek, Lia, Berkhout, Ben, Stefan Pöhlmann, Amsterdam institute for Infection and Immunity, and Medical Microbiology
Published: 2006

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