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1. Correction to: In Vitro Seeding Activity of Glycoform-Deficient Prions from Variably Protease-Sensitive Prionopathy and Familial CJD Associated with PrPV180I Mutation

Author

Jan P. M. Langeveld, Wen-Quan Zou, Mohammed Moudjou, Romany Abskharon, Jiachun Feng, Zerui Wang, Ling Xu, Tetsuyuki Kitamoto, Brian S. Appleby, Robert B. Petersen, Qingzhong Kong, Jiafeng Chen, Pingping Shen, Johnny Dang, Hyoung Gon Lee, Li Cui, Alise Adornato, Jue Yuan, Yong-Sun Kim, Jiyan Ma, Yue Lang, Jilin University (JLU), The first hospital of Jilin University, Case Western Reserve University [Cleveland], Center for Neurodegenerative Science, Van Andel Research Institute, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tohoku University [Sendai], Tohoku University Graduate School of Medicine, Department of Biology (Texas State University), Texas State University, Hallym University College of Medicine, Wageningen BioVeterinary Research, Wageningen University and Research [Wageningen] (WUR), National Prion Disease Pathology Surveillance Center, Department of Neurology University Hospitals of Cleveland Case Western Reserve University Cleveland, Central Michigan University College of Medicine Foundation Sciences, Partenaires INRAE, Vrije Universiteit Brussel (VUB), College of Engineering [Beijing], China Agricultural University (CAU), Department of Pathology, Wageningen University and Research Centre (WUR), Department of Molecular and Cellular Biochemistry, Ohio State University [Columbus] (OSU), Hanyang University, Department of Neurology, The First Hospital of Jilin University, Case Western Reserve University School of Medicine, Center for Neurodegenerative Science, Van Andel Research Institute, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Center for Prion Diseases, Department of Biology, College of Sciences, The University of Texas at San Antonio (UTSA)-The University of Texas at San Antonio (UTSA), Department of Microbiology, College of Medicine, Hallym University-Hallym University, Foundation Sciences, Partenaires INRAE-Partenaires INRAE, State Key Laboratory for Infectious Disease prevention and Control, Beijing Institute of Technology (BIT), and United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS)R21 NS096626R01 NS088604R01 NS109532

Subjects
Protein Folding, Glycosylation, [SDV]Life Sciences [q-bio], Neuroscience (miscellaneous), Variably protease-sensitive prionopathy, Mice, Transgenic, Molecular neuroscience, Biology, Creutzfeldt-Jakob Syndrome, Prion Proteins, Substrate Specificity, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Life Science, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Host Pathogen Interaction & Diagnostics, 0303 health sciences, [SCCO.NEUR]Cognitive science/Neuroscience, Bacteriologie, Correction, Brain, Bacteriology, Bacteriology, Host Pathogen Interaction & Diagnostics, Molecular biology, In vitro, Host Pathogen Interactie & Diagnostiek, 3. Good health, Neurology, Mutation (genetic algorithm), Bacteriologie, Host Pathogen Interactie & Diagnostiek, Mutation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030217 neurology & neurosurgery, Peptide Hydrolases
Abstract

International audience; The original version of this article unfortunately contained a mistake. The email address Dr. Wen-Quan Zou, one of the corresponding authors should be written as wxz6@case.edu instead of wxz@case.edu.

Published
2019
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2. Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis

Author

Hemelaar, Joris, Elangovan, Ramyiadarsini, Yun, Jason, Dickson-Tetteh, Leslie, Fleminger, Isabella, Kirtley, Shona, Williams, Brian, Gouws-Williams, Eleanor, Ghys, Peter D, Abimiku, Alash'le G, Agwale, Simon, Archibald, Chris, Avidor, Boaz, Barbás, María Gabriela, Barre-Sinoussi, Francoise, Barugahare, Banson, Belabbes, El Hadj, Bertagnolio, Silvia, Birx, Deborah, Bobkov, Aleksei F, Brandful, James, Bredell, Helba, Brennan, Catherine A, Brooks, James, Bruckova, Marie, Buonaguro, Luigi, Buonaguro, Franco, Buttò, Stefano, Buve, Anne, Campbell, Mary, Carr, Jean, Carrera, Alex, Carrillo, Manuel Gómez, Celum, Connie, Chaplin, Beth, Charles, Macarthur, Chatzidimitriou, Dimitrios, Chen, Zhiwei, Chijiwa, Katsumi, Cooper, David, Cunningham, Philip, Dagnra, Anoumou, de Gascun, Cillian F, Del Amo, Julia, Delgado, Elena, Dietrich, Ursula, Dwyer, Dominic, Ellenberger, Dennis, Ensoli, Barbara, Essex, Max, Gao, Feng, Fleury, Herve, Fonjungo, Peter N, Foulongne, Vincent, Gadkari, Deepak A, García, Federico, Garsia, Roger, Gershy-Damet, Guy Michel, Glynn, Judith R, Goodall, Ruth, Grossman, Zehava, Lindenmeyer-Guimarães, Monick, Hahn, Beatrice, Hamers, Raph L, Hamouda, Osamah, Handema, Ray, He, Xiang, Herbeck, Joshua, Ho, David D, Holguin, Africa, Hosseinipour, Mina, Hunt, Gillian, Ito, Masahiko, Bel Hadj Kacem, Mohamed Ali, Kahle, Erin, Kaleebu, Pontiano Kaleebu, Kalish, Marcia, Kamarulzaman, Adeeba, Kang, Chun, Kanki, Phyllis, Karamov, Edward, Karasi, Jean-Claude, Kayitenkore, Kayitesi, Kelleher, Tony, Kitayaporn, Dwip, Kostrikis, Leondios G, Kucherer, Claudia, Lara, Claudia, Leitner, Thomas, Liitsola, Kirsi, Lingappa, Jai, Linka, Marek, Lorenzana de Rivera, Ivette, Lukashov, Vladimir, Maayan, Shlomo, Mayr, Luzia, McCutchan, Francine, Meda, Nicolas, Menu, Elisabeth, Mhalu, Fred, Mloka, Doreen, Mokili, John L, Montes, Brigitte, Mor, Orna, Morgado, Mariza, Mosha, Fausta, Moussi, Awatef, Mullins, James, Najera, Rafael, Nasr, Mejda, Ndembi, Nicaise, Neilson, Joel R, Nerurkar, Vivek R, Neuhann, Florian, Nolte, Claudine, Novitsky, Vlad, Nyambi, Philippe, Ofner, Marianna, Paladin, Fem J, Papa, Anna, Pape, Jean, Parkin, Neil, Parry, Chris, Peeters, Martine, Pelletier, Alexandra, Pérez-Álvarez, Lucía, Pillay, Deenan, Pinto, Angie, Quang, Trinh Duy, Rademeyer, Cecilia, Raikanikoda, Filimone, Rayfield, Mark A, Reynes, Jean-Marc, Rinke de Wit, Tobias, Robbins, Kenneth E, Rolland, Morgane, Rousseau, Christine, Salazar-Gonzales, Jesus, Salem, Hanan, Salminen, Mika, Salomon, Horacio, Sandstrom, Paul, Santiago, Mario L, Sarr, Abdoulaye D, Schroeder, Bryan, Segondy, Michel, Selhorst, Philippe, Sempala, Sylvester, Servais, Jean, Shaik, Ansari, Shao, Yiming, Slim, Amine, Soares, Marcelo A, Songok, Elijah, Stewart, Debbie, Stokes, Julie, Subbarao, Shambavi, Sutthent, Ruengpung, Takehisa, Jun, Tanuri, Amilcar, Tee, Kok Keng, Thapa, Kiran, Thomson, Michael, Tran, Tyna, Urassa, Willy, Ushijima, Hiroshi, van de Perre, Philippe, van der Groen, Guido, van Laethem, Kristel, van Oosterhout, Joep, van Sighem, Ard, van Wijngaerden, Eric, Vandamme, Anne-Mieke, Vercauteren, Jurgen, Vidal, Nicole, Wallace, Lesley, Williamson, Carolyn, Wolday, Dawit, Xu, Jianqing, Yang, Chunfu, Zhang, Linqi, Zhang, Rong, John Radcliffe Hospital [Oxford University Hospital], Centre for Statistics in Medicine, University of Oxford [Oxford], Stellenbosch University, UNAIDS [Genève, Suisse] (ONUSIDA), Institut Pasteur [Paris], Noguchi Memorial Institute for Medical Research [Accra, Ghana] (NMIMR), University of Ghana, Institute of Tropical Medicine [Antwerp] (ITM), State Key Laboratory of Silkworm Genome Biology, Southwest University, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Georg-Speyer-Haus, The University of Sydney, National AIDS Centre, Istituto Superiore di Sanita [Rome], Harvard School of Public Health, Digital Enterprise Research Institute (DERI-NUIG), National University of Ireland [Galway] (NUI Galway), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Departments of Medicine and Microbiology, University of Alabama at Birmingham [ Birmingham] (UAB), Robert Koch Institute [Berlin] (RKI), Beihang University (BUAA), Statens Serum Institut [Copenhagen], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), SANTE/SIDA [Bobo-Dioulasso, Burkina Faso], Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Department of Microbiology, University of Washington School of Medicine, Department of Microbiology, Medical School, University of Thessaly [Volos] (UTH), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Africa Centre for Health and Population Studies, University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Lab-STICC_UBO_CID_IHSEV, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), State Key Laboratory of Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Laboratory of Virology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Universidade Federal do Rio de Janeiro (UFRJ), Departements of Medicine and Microbiology, University of Alabama [Tuscaloosa] (UA), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Département Génétique Internal Médecine, Hôpital Universitaire Leuven, Department of Chemical and Biomolecular Engineering [Baltimore], Johns Hopkins University (JHU), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, China Academy of Chinese Medical Sciences, Chatzidimitriou, Dimitrios [0000-0001-9656-5898], University of Oxford, Institut Pasteur [Paris] (IP), Istituto Superiore di Sanità (ISS), Microbiologie Fondamentale et Pathogénicité (MFP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), UNAIDS, Noguchi Memorial Institute for Medical Research, University of Ghana, Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Beihang University, Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Nuffield Department of Women's and Reproductive Health (NDWRH), University of Oxford- John Radcliffe Hospital [Oxford University Hospital], South African Centre for Epidemiological Modelling and Analysis, JH is supported by the Oxford University Clinical Academic Graduate School (Oxford, UK) and Linacre College, Oxford University (Oxford, UK)., WHO–UNAIDS Network for HIV Isolation Characterisation : Alash'le G Abimiku, Simon Agwale, Chris Archibald, Boaz Avidor, María Gabriela Barbás, Francoise Barre-Sinoussi, Banson Barugahare, El Hadj Belabbes, Silvia Bertagnolio, Deborah Birx, Aleksei F Bobkov, James Brandful, Helba Bredell, Catherine A Brennan, James Brooks, Marie Bruckova, Luigi Buonaguro, Franco Buonaguro, Stefano Buttò, Anne Buve, Mary Campbell, Jean Carr, Alex Carrera, Manuel Gómez Carrillo, Connie Celum, Beth Chaplin, Macarthur Charles, Dimitrios Chatzidimitriou, Zhiwei Chen, Katsumi Chijiwa, David Cooper, Philip Cunningham, Anoumou Dagnra, Cillian F de Gascun, Julia Del Amo, Elena Delgado, Ursula Dietrich, Dominic Dwyer, Dennis Ellenberger, Barbara Ensoli, Max Essex, Feng Gao, Herve Fleury, Peter N Fonjungo, Vincent Foulongne, Deepak A Gadkari, Federico García, Roger Garsia, Guy Michel Gershy-Damet, Judith R Glynn, Ruth Goodall, Zehava Grossman, Monick Lindenmeyer-Guimarães, Beatrice Hahn, Raph L Hamers, Osamah Hamouda, Ray Handema, Xiang He, Joshua Herbeck, David D Ho, Africa Holguin, Mina Hosseinipour, Gillian Hunt, Masahiko Ito, Mohamed Ali Bel Hadj Kacem, Erin Kahle, Pontiano Kaleebu Kaleebu, Marcia Kalish, Adeeba Kamarulzaman, Chun Kang, Phyllis Kanki, Edward Karamov, Jean-Claude Karasi, Kayitesi Kayitenkore, Tony Kelleher, Dwip Kitayaporn, Leondios G Kostrikis, Claudia Kucherer, Claudia Lara, Thomas Leitner, Kirsi Liitsola, Jai Lingappa, Marek Linka, Ivette Lorenzana de Rivera, Vladimir Lukashov, Shlomo Maayan, Luzia Mayr, Francine McCutchan, Nicolas Meda, Elisabeth Menu, Fred Mhalu, Doreen Mloka, John L Mokili, Brigitte Montes, Orna Mor, Mariza Morgado, Fausta Mosha, Awatef Moussi, James Mullins, Rafael Najera, Mejda Nasr, Nicaise Ndembi, Joel R Neilson, Vivek R Nerurkar, Florian Neuhann, Claudine Nolte, Vlad Novitsky, Philippe Nyambi, Marianna Ofner, Fem J Paladin, Anna Papa, Jean Pape, Neil Parkin, Chris Parry, Martine Peeters, Alexandra Pelletier, Lucía Pérez-Álvarez, Deenan Pillay, Angie Pinto, Trinh Duy Quang, Cecilia Rademeyer, Filimone Raikanikoda, Mark A Rayfield, Jean-Marc Reynes, Tobias Rinke de Wit, Kenneth E Robbins, Morgane Rolland, Christine Rousseau, Jesus Salazar-Gonzales, Hanan Salem, Mika Salminen, Horacio Salomon, Paul Sandstrom, Mario L Santiago, Abdoulaye D Sarr, Bryan Schroeder, Michel Segondy, Philippe Selhorst, Sylvester Sempala, Jean Servais, Ansari Shaik, Yiming Shao, Amine Slim, Marcelo A Soares, Elijah Songok, Debbie Stewart, Julie Stokes, Shambavi Subbarao, Ruengpung Sutthent, Jun Takehisa, Amilcar Tanuri, Kok Keng Tee, Kiran Thapa, Michael Thomson, Tyna Tran, Willy Urassa, Hiroshi Ushijima, Philippevan de Perre, Guidovan der Groen, Kristel van Laethem, Joep van Oosterhout, Ard van Sighem, Eric van Wijngaerden, Anne-Mieke Vandamme, Jurgen Vercauteren, Nicole Vidal, Lesley Wallace, Carolyn Williamson, Dawit Wolday, Jianqing Xu, Chunfu Yang, Linqi Zhang, and Rong Zhang

Subjects
0301 basic medicine, Serotype, Genotype, Genotyping Techniques, 030106 microbiology, DIVERSITY, MULTICENTER, VACCINE, HIV Infections, Genome, Viral, Biology, Global Health, Serogroup, SUBTYPES, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, INFECTION, Genetic variation, Global health, Humans, HIV vaccine, Serotyping, AIDS Vaccines, Science & Technology, Molecular epidemiology, Genetic Variation, Subtyping, 3. Good health, Trend analysis, 030104 developmental biology, Infectious Diseases, 13. Climate action, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Life Sciences & Biomedicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None. ispartof: LANCET INFECTIOUS DISEASES vol:19 issue:2 pages:143-155 ispartof: location:United States status: published

Published
2018
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3. Potent and Broad Anti-HIV-1 Activity Exhibited by a Glycosyl-Phosphatidylinositol-Anchored Peptide Derived from the CDR H3 of Broadly Neutralizing Antibody PG16▿†‡

Author

Shumei Wang, Linqi Zhang, Lihong Liu, Mengran Qian, Jason T. Kimata, Lifei Yang, Paul Zhou, Michael Wen, Yong Liu, Weiming Wang, Yiming Shao, Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), State Key Laboratory of Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Department of Molecular Virology and Microbiology, Baylor College of Medicine (BCM), and Baylor University-Baylor University

Subjects
CD4-Positive T-Lymphocytes, medicine.drug_class, Glycosylphosphatidylinositols, Recombinant Fusion Proteins, Immunology, Gene Expression, Peptide, chemical and pharmacologic phenomena, Biology, HIV Antibodies, Monoclonal antibody, Microbiology, Neutralization, Epitope, Cell Line, Fusion gene, 03 medical and health sciences, Virology, mental disorders, Vaccines and Antiviral Agents, medicine, Humans, Cloning, Molecular, Lipid raft, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, 030306 microbiology, Glycopeptides, Virus Internalization, Molecular biology, Antibodies, Neutralizing, 3. Good health, Protein Structure, Tertiary, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Cell culture, Insect Science, biology.protein, HIV-1, lipids (amino acids, peptides, and proteins), Antibody
Abstract

PG9 and PG16 are two recently isolated quaternary-specific human monoclonal antibodies that neutralize 70 to 80% of circulating HIV-1 isolates. The crystal structure of PG16 shows that it contains an exceptionally long CDR H3 that forms a unique stable subdomain that towers above the antibody surface to confer fine specificity. To determine whether this unique architecture of CDR H3 itself is sufficient for epitope recognition and neutralization, we cloned CDR H3 subdomains derived from human monoclonal antibodies PG16, PG9, b12, E51, and AVF and genetically linked them to a glycosyl-phosphatidylinositol (GPI) attachment signal. Each fusion gene construct is expressed and targeted to lipid rafts of plasma membranes through a GPI anchor. Moreover, GPI-CDR H3(PG16, PG9, and E51), but not GPI-CDR H3(b12 and AVF), specifically neutralized multiple clades of HIV-1 isolates with a great degree of potency when expressed on the surface of transduced TZM-bl cells. Furthermore, GPI-anchored CDR H3(PG16), but not GPI-anchored CDR H3(AVF), specifically confers resistance to HIV-1 infection when expressed on the surface of transduced human CD4 + T cells. Finally, the CDR H3 mutations (Y100HF, D100IA, and G7) that were previously shown to compromise the neutralization activity of antibody PG16 also abolished the neutralization activity of GPI-CDR H3(PG16). Thus, we conclude that the CDR H3 subdomain of PG16 neutralizes HIV-1 when targeted to the lipid raft of the plasma membrane of HIV-1-susceptible cells and that GPI-CDR H3 can be an alternative approach for determining whether the CDR H3 of certain antibodies alone can exert epitope recognition and neutralization.

Published
2011
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