41 results on '"Berkhout, Ben"'
Search Results
2. Persistent HIV-1 transcription during ART: time to reassess its significance?
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Fombellida-Lopez, Céline, Berkhout, Ben, Darcis, Gilles, and Pasternak, Alexander O.
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- 2024
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3. Novel role of UHRF1 in the epigenetic repression of the latent HIV-1
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Verdikt, Roxane, Bendoumou, Maryam, Bouchat, Sophie, Nestola, Lorena, Pasternak, Alexander O, Darcis, Gilles, Avettand-Fenoel, Véronique, Vanhulle, Caroline, Aït-Ammar, Amina, Santangelo, Marion, Plant, Estelle, Le Douce, Valentin, Delacourt, Nadège, Cicilionytė, Aurelija, Necsoi, Coca, Corazza, Francis, Passaes, Caroline Pereira Bittencourt, Schwartz, Christian, Bizet, Martin, Fuks, François, Sáez-Cirión, Asier, Rouzioux, Christine, De Wit, Stéphane, Berkhout, Ben, Gautier, Virginie, Rohr, Olivier, and Van Lint, Carine
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Genetics ,HIV/AIDS ,Infectious Diseases ,2.1 Biological and endogenous factors ,Aetiology ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,Acquired Immunodeficiency Syndrome ,CCAAT-Enhancer-Binding Proteins ,DNA Methylation ,Decitabine ,Epigenetic Repression ,HIV Infections ,HIV-1 ,Humans ,Ubiquitin-Protein Ligases ,Virus Latency ,HIV-1 latency ,Reactivation ,UHRF1 ,Epigenetics ,EGCG ,Clinical Sciences ,Public Health and Health Services ,Clinical sciences ,Epidemiology - Abstract
BackgroundThe multiplicity, heterogeneity, and dynamic nature of human immunodeficiency virus type-1 (HIV-1) latency mechanisms are reflected in the current lack of functional cure for HIV-1. Accordingly, all classes of latency-reversing agents (LRAs) have been reported to present variable ex vivo potencies. Here, we investigated the molecular mechanisms underlying the potency variability of one LRA: the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC).MethodsWe employed epigenetic interrogation methods (electrophoretic mobility shift assays, chromatin immunoprecipitation, Infinium array) in complementary HIV-1 infection models (latently-infected T-cell line models, primary CD4+ T-cell models and ex vivo cultures of PBMCs from HIV+ individuals). Extracellular staining of cell surface receptors and intracellular metabolic activity were measured in drug-treated cells. HIV-1 expression in reactivation studies was explored by combining the measures of capsid p24Gag protein, green fluorescence protein signal, intracellular and extracellular viral RNA and viral DNA.FindingsWe uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) to the HIV-1 promoter. We showed that UHRF1 redundantly binds to the HIV-1 promoter with different binding modalities where DNA methylation was either non-essential, essential or enhancing UHRF1 binding. We further demonstrated the role of UHRF1 in the epigenetic repression of the latent viral promoter by a concerted control of DNA and histone methylations.InterpretationA better understanding of the molecular mechanisms of HIV-1 latency allows for the development of innovative antiviral strategies. As a proof-of-concept, we showed that pharmacological inhibition of UHRF1 in ex vivo HIV+ patient cell cultures resulted in potent viral reactivation from latency. Together, we identify UHRF1 as a novel actor in HIV-1 epigenetic silencing and highlight that it constitutes a new molecular target for HIV-1 cure strategies.FundingFunding was provided by the Belgian National Fund for Scientific Research (F.R.S.-FNRS, Belgium), the « Fondation Roi Baudouin », the NEAT (European AIDS Treatment Network) program, the Internationale Brachet Stiftung, ViiV Healthcare, the Télévie, the Walloon Region (« Fonds de Maturation »), « Les Amis des Instituts Pasteur à Bruxelles, asbl », the University of Brussels (Action de Recherche Concertée ULB grant), the Marie Skodowska Curie COFUND action, the European Union's Horizon 2020 research and innovation program under grant agreement No 691119-EU4HIVCURE-H2020-MSCA-RISE-2015, the French Agency for Research on AIDS and Viral Hepatitis (ANRS), the Sidaction and the "Alsace contre le Cancer" Foundation. This work is supported by 1UM1AI164562-01, co-funded by National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases.
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- 2022
4. In-house ELISA protocols for capsid p24 detection of diverse HIV isolates
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Molina, Mariano A., Vink, Monique, Berkhout, Ben, and Herrera-Carrillo, Elena
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- 2023
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5. HIV co-opts a cellular antiviral mechanism, activation of stress kinase PKR by its RNA, to enable splicing of rev/tat mRNA
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Namer, Lise Sarah, Harwig, Alex, Heynen, Stephan P., Das, Atze T., Berkhout, Ben, and Kaempfer, Raymond
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- 2023
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6. AAV vectors displaying bispecific DARPins enable dual-control targeted gene delivery
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Theuerkauf, Samuel A., Herrera-Carrillo, Elena, John, Fabian, Zinser, Luca J., Molina, Mariano A., Riechert, Vanessa, Thalheimer, Frederic B., Börner, Kathleen, Grimm, Dirk, Chlanda, Petr, Berkhout, Ben, and Buchholz, Christian J.
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- 2023
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7. CRISPR-Cas12b enables a highly efficient attack on HIV proviral DNA in T cell cultures
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Fan, Minghui, Bao, Yuanling, Berkhout, Ben, and Herrera-Carrillo, Elena
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- 2023
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8. ‘Zombie’ proviruses in the spotlight: exploring the dark side of HIV persistence
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Pasternak, Alexander O., Tsukamoto, Tetsuo, and Berkhout, Ben
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- 2023
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9. FcγRIIA-specific DARPins as novel tools in blood cell analysis and platelet aggregation
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Riechert, Vanessa, Hein, Sascha, Visser, Mayken, Zimmermann, Mathias, Wesche, Jan, Adams, Philipp A., Theuerkauf, Samuel A., Jamali, Arezoo, Wangorsch, Andrea, Reuter, Andreas, Pasternak, Alexander O., Hartmann, Jessica, Greinacher, Andreas, Herrera-Carrillo, Elena, Berkhout, Ben, Cichutek, Klaus, and Buchholz, Christian J.
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- 2023
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10. HIV persistence: silence or resistance?
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Pasternak, Alexander O and Berkhout, Ben
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- 2023
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11. CRISPR-Cas-Based Gene Therapy to Target Viral Infections
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Hussein, Mouraya, Berkhout, Ben, Herrera-Carrillo, Elena, Yun, Yang H., editor, and Yoder, Kristine E., editor
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- 2022
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12. Reverse transcription of HIV-1 2-LTR circle transcripts does frequently cause 3'-polypurine tract mutations implicated in dolutegravir resistance
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Dekker, José G., primary, Klaver, Bep, additional, Berkhout, Ben, additional, and Das, Atze T., additional
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- 2024
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13. Towards a molecular profile of antiretroviral therapy-free HIV remission
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Adams, Philipp, Berkhout, Ben, and Pasternak, Alexander O.
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- 2022
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14. CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA
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Liu, Ye, primary, Binda, Caroline S., additional, Berkhout, Ben, additional, and Das, Atze T., additional
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- 2023
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15. PA-305 FC gamma receptor gene polymorphisms and reservoir size in HIV patients in Ghana
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Lamptey, Helena, primary, Pasternak, Alexander O, additional, Bonney, Evelyn Y, additional, Aboagye, James O, additional, Boateng, Anthony T, additional, Abana, Christopher ZY, additional, Adams, Philipp, additional, Cicilionyte, Aurelija, additional, Berkhout, Ben, additional, Adu, Bright, additional, and Kyei, George B, additional
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- 2023
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16. Integration of SARS-CoV-2 RNA in infected human cells by retrotransposons: an unlikely hypothesis and old viral relationships
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Grandi, Nicole, Tramontano, Enzo, and Berkhout, Ben
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- 2021
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17. Recent Advances Using Genetic Therapies Against Infectious Diseases and for Vaccination
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Galy, Anne, primary, Berkhout, Ben, additional, Breckpot, Karine, additional, Pichon, Chantal, additional, Bloom, Kristie, additional, Kiem, Hans-Peter, additional, Mühlebach, Michael D., additional, and McCune, Joseph M., additional
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- 2023
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18. HIV-1 3′-Polypurine Tract Mutations Confer Dolutegravir Resistance by Switching to an Integration-Independent Replication Mechanism via 1-LTR Circles
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Dekker, José G., primary, Klaver, Bep, additional, Berkhout, Ben, additional, and Das, Atze T., additional
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- 2023
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19. Data from Construction of a Minimal HIV-1 Variant that Selectively Replicates in Leukemic Derived T-Cell Lines: Towards a New Virotherapy Approach
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Jeeninga, Rienk E., primary, Jan, Barbara, primary, van der Linden, Birgit, primary, van den Berg, Henk, primary, and Berkhout, Ben, primary
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- 2023
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20. Supplementary Figure 1 from Construction of a Minimal HIV-1 Variant that Selectively Replicates in Leukemic Derived T-Cell Lines: Towards a New Virotherapy Approach
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Jeeninga, Rienk E., primary, Jan, Barbara, primary, van der Linden, Birgit, primary, van den Berg, Henk, primary, and Berkhout, Ben, primary
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- 2023
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21. Efficient CRISPR-Cas13d-Based Antiviral Strategy to Combat SARS-CoV-2
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Hussein, Mouraya, primary, Andrade dos Ramos, Zaria, additional, Vink, Monique A., additional, Kroon, Pascal, additional, Yu, Zhenghao, additional, Enjuanes, Luis, additional, Zuñiga, Sonia, additional, Berkhout, Ben, additional, and Herrera-Carrillo, Elena, additional
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- 2023
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22. A CRISPR-Cas Cure for HIV/AIDS
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Hussein, Mouraya, primary, Molina, Mariano A., additional, Berkhout, Ben, additional, and Herrera-Carrillo, Elena, additional
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- 2023
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23. 137 FcγRIIa-specific DARPins as a novel tool toward specific gene delivery into HIV reservoir cells
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Jamali, Arezoo, primary, Riechert, Vanessa, additional, Theuerkauf, Samuel, additional, Hein, Sascha, additional, Adams, Philipp, additional, Herreracarrillo, Elena, additional, Berkhout, Ben, additional, Cichutek, Klaus, additional, Hartmann, Jessica, additional, and Buchholz, Christian, additional
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- 2022
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24. Silent codon positions in the A-rich HIV RNA genome that do not easily become A: Restrictions imposed by the RNA sequence and structure
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Berkhout, Ben, primary and van Hemert, Formijn J, additional
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- 2022
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25. HIV-phyloTSI: Subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data
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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
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[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.
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- 2022
26. 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))
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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
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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.
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- 2022
27. A combinatorial CRISPR-Cas12a attack on HIV DNA
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Fan, Minghui, primary, Berkhout, Ben, additional, and Herrera-Carrillo, Elena, additional
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- 2022
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28. Novel role of UHRF1 in the epigenetic repression of the latent HIV-1
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Verdikt, Roxane, primary, Bendoumou, Maryam, additional, Bouchat, Sophie, additional, Nestola, Lorena, additional, Pasternak, Alexander O., additional, Darcis, Gilles, additional, Avettand-Fenoel, Véronique, additional, Vanhulle, Caroline, additional, Aït-Ammar, Amina, additional, Santangelo, Marion, additional, Plant, Estelle, additional, Douce, Valentin Le, additional, Delacourt, Nadège, additional, Cicilionytė, Aurelija, additional, Necsoi, Coca, additional, Corazza, Francis, additional, Passaes, Caroline Pereira Bittencourt, additional, Schwartz, Christian, additional, Bizet, Martin, additional, Fuks, François, additional, Sáez-Cirión, Asier, additional, Rouzioux, Christine, additional, De Wit, Stéphane, additional, Berkhout, Ben, additional, Gautier, Virginie, additional, Rohr, Olivier, additional, and Van Lint, Carine, additional
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- 2022
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29. SARS-CoV-2 Evolution: On the Sudden Appearance of the Omicron Variant
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Berkhout, Ben, primary and Herrera-Carrillo, Elena, additional
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- 2022
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30. A highly virulent variant of HIV-1 circulating in the Netherlands
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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
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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.
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31. Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load
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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
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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.
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32. Impact of the size of CRISPR-Cas gene cassettes on the packaging efficiency and transduction titer of lentiviral vectors
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Fan, Minghui, primary, Berkhout, Ben, additional, and Herrera-Carrillo, Elena, additional
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33. In Silico Prediction and Selection of Target Sequences in the SARS-CoV-2 RNA Genome for an Antiviral Attack
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Hussein, Mouraya, primary, Andrade dos Ramos, Zaria, additional, Berkhout, Ben, additional, and Herrera-Carrillo, Elena, additional
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34. Mutations in the HIV-1 3′-Polypurine Tract Can Confer Dolutegravir Resistance
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Dekker, José G., primary, Klaver, Bep, additional, Berkhout, Ben, additional, and Das, Atze T., additional
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- View/download PDF
35. Transient CRISPR-Cas Treatment Can Prevent Reactivation of HIV-1 Replication in a Latently Infected T-Cell Line
- Author
-
Liu, Ye, primary, Jeeninga, Rienk E., additional, Klaver, Bep, additional, Berkhout, Ben, additional, and Das, Atze T., additional
- Published
- 2021
- Full Text
- View/download PDF
36. Early Effects of HTLV-1 Infection on the Activation, Exhaustion, and Differentiation of T-Cells in Humanized NSG Mice
- Author
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Espíndola, Otávio de Melo, primary, Siteur-van Rijnstra, Esther, additional, Frankin, Esmay, additional, Weijer, Kees, additional, van der Velden, Yme Ubeles, additional, Berkhout, Ben, additional, Blom, Bianca, additional, and Villaudy, Julien, additional
- Published
- 2021
- Full Text
- View/download PDF
37. The Splice of Life: Does RNA Processing Have a Role in HIV-1 Persistence?
- Author
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Pasternak, Alexander O., primary and Berkhout, Ben, additional
- Published
- 2021
- Full Text
- View/download PDF
38. Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy.
- Author
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Pasternak, Alexander O., Vroom, Jelmer, Kootstra, Neeltje A., Wit, Ferdinand WNM, de Bruin, Marijn, De Francesco, Davide, Bakker, Margreet, Sabin, Caroline A., Winston, Alan, Prins, Jan M., Reiss, Peter, and Berkhout, Ben
- Published
- 2021
- Full Text
- View/download PDF
39. CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA.
- Author
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Ye Liu, Binda, Caroline S., Berkhout, Ben, and Das, Atze T.
- Subjects
- *
CRISPRS , *DNA primers , *DNA , *GENOME editing , *HIV , *CELL transformation - Abstract
Several studies indicate that CRISPR-Cas gene-editing systems can be used to inactivate the HIV-1 proviral DNA in infected cells. Such gene editing introduces mutations, mostly small insertions and deletions (indels), at the targeted sites in the HIV genome or causes excision or inversion of the proviral DNA fragment between two target sites. To investigate whether CRISPR-Cas treatment of latently infected T cell lines can also cause large unintended deletions, we designed a PCR-based sequencing strategy with primer binding sites at various positions in the chromosomal DNA surrounding the integrated proviral DNA genome. We, here, demonstrate that both continuous and transient CRISPR-Cas attack on the integrated HIV DNA does not only result in the expected small indels, but also frequently causes much larger deletions that can include flanking cellular DNA sequences. Analysis of the breakpoint junction sites indicates that the deletions were triggered by an initial on-target attack by CRISPR-Cas. Upon continuous CRISPR-Cas treatment, small microhomologies were frequently observed at the junction sites, which indicates that microhomology-mediated end-joining DNA repair is involved in the generation of the large deletions. As the loss of chromosomal sequences may cause oncogenic cell transformation, unintended large deletions form a potential safety risk in clinical application of this antiviral application. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
40. Correction: HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry.
- Author
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Eggink D, Bontjer I, de Taeye SW, Langedijk JPM, Berkhout B, and Sanders RW
- Published
- 2022
- Full Text
- View/download PDF
41. A highly virulent variant of HIV-1 circulating in the Netherlands.
- Author
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Wymant C, Bezemer D, Blanquart F, Ferretti L, Gall A, Hall M, Golubchik T, Bakker M, Ong SH, Zhao L, Bonsall D, de Cesare M, MacIntyre-Cockett G, Abeler-Dörner L, Albert J, Bannert N, Fellay J, Grabowski MK, Gunsenheimer-Bartmeyer B, Günthard HF, Kivelä P, Kouyos RD, Laeyendecker O, Meyer L, Porter K, Ristola M, van Sighem A, Berkhout B, Kellam P, Cornelissen M, Reiss P, and Fraser C
- Subjects
- Adult, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Evolution, Molecular, Female, Genome, Viral, Genotype, HIV Infections drug therapy, HIV Infections immunology, HIV Infections transmission, HIV-1 genetics, HIV-1 physiology, Humans, Male, Mutation, Netherlands, Phylogeny, Viral Load, Virulence, HIV Infections virology, HIV-1 pathogenicity
- Abstract
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
- Full Text
- View/download PDF
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