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  • 1
    Publication Date: 2015-08-26
    Description: T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2009-02-27
    Description: The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from 〉2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P 〈 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148020/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148020/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawashima, Yuka -- Pfafferott, Katja -- Frater, John -- Matthews, Philippa -- Payne, Rebecca -- Addo, Marylyn -- Gatanaga, Hiroyuki -- Fujiwara, Mamoru -- Hachiya, Atsuko -- Koizumi, Hirokazu -- Kuse, Nozomi -- Oka, Shinichi -- Duda, Anna -- Prendergast, Andrew -- Crawford, Hayley -- Leslie, Alasdair -- Brumme, Zabrina -- Brumme, Chanson -- Allen, Todd -- Brander, Christian -- Kaslow, Richard -- Tang, James -- Hunter, Eric -- Allen, Susan -- Mulenga, Joseph -- Branch, Songee -- Roach, Tim -- John, Mina -- Mallal, Simon -- Ogwu, Anthony -- Shapiro, Roger -- Prado, Julia G -- Fidler, Sarah -- Weber, Jonathan -- Pybus, Oliver G -- Klenerman, Paul -- Ndung'u, Thumbi -- Phillips, Rodney -- Heckerman, David -- Harrigan, P Richard -- Walker, Bruce D -- Takiguchi, Masafumi -- Goulder, Philip -- 1 R01 AI067073/AI/NIAID NIH HHS/ -- G0500384/Medical Research Council/United Kingdom -- G0501777/Medical Research Council/United Kingdom -- G108/626/Medical Research Council/United Kingdom -- R01 AI046995/AI/NIAID NIH HHS/ -- R01 AI046995-10/AI/NIAID NIH HHS/ -- R01 AI060460/AI/NIAID NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI064060-06A1/AI/NIAID NIH HHS/ -- R01AI46995/AI/NIAID NIH HHS/ -- R01AI64060/AI/NIAID NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 2;458(7238):641-5. doi: 10.1038/nature07746. Epub 2009 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242411" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Epitopes, T-Lymphocyte/chemistry/genetics/immunology ; HIV Antigens/chemistry/genetics/immunology ; HIV-1/genetics/*immunology/physiology ; HLA-B Antigens/genetics/*immunology ; Humans ; Internationality ; Leukocytes/*immunology ; Polymorphism, Genetic ; gag Gene Products, Human Immunodeficiency Virus/chemistry/genetics/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-07-12
    Description: Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naive recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289910/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carlson, Jonathan M -- Schaefer, Malinda -- Monaco, Daniela C -- Batorsky, Rebecca -- Claiborne, Daniel T -- Prince, Jessica -- Deymier, Martin J -- Ende, Zachary S -- Klatt, Nichole R -- DeZiel, Charles E -- Lin, Tien-Ho -- Peng, Jian -- Seese, Aaron M -- Shapiro, Roger -- Frater, John -- Ndung'u, Thumbi -- Tang, Jianming -- Goepfert, Paul -- Gilmour, Jill -- Price, Matt A -- Kilembe, William -- Heckerman, David -- Goulder, Philip J R -- Allen, Todd M -- Allen, Susan -- Hunter, Eric -- 2P51RR000165-51/RR/NCRR NIH HHS/ -- G108/626/Medical Research Council/United Kingdom -- OD P51OD11132/OD/NIH HHS/ -- P01-AI074415/AI/NIAID NIH HHS/ -- P30 AI050409/AI/NIAID NIH HHS/ -- P51 OD010425/OD/NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- P51RR165/RR/NCRR NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI64060/AI/NIAID NIH HHS/ -- R37 AI051231/AI/NIAID NIH HHS/ -- R37 AI51231/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- T32-AI007387/AI/NIAID NIH HHS/ -- U01 AI 66454/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):1254031. doi: 10.1126/science.1254031. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microsoft Research, Redmond, WA 98052, USA. carlson@microsoft.com ehunte4@emory.edu. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. ; Microsoft Research, Redmond, WA 98052, USA. ; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 7BN, UK. National Institute of Health Research, Oxford Biomedical Research Centre, Oxford OX3 7LE, UK. Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany. ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ; International AIDS Vaccine Initiative, London SW10 9NH, UK. Imperial College of Science Technology and Medicine, London SW10 9NH, UK. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94105, USA. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. ; Microsoft Research, Los Angeles, CA 98117, USA. ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Microsoft Research, Los Angeles, CA 98117, USA. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. carlson@microsoft.com ehunte4@emory.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013080" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Consensus Sequence ; DNA Mutational Analysis ; Disease Transmission, Infectious/statistics & numerical data ; Female ; HIV Infections/*transmission ; HIV-1/*genetics ; *Heterosexuality ; High-Throughput Nucleotide Sequencing ; Human Immunodeficiency Virus Proteins/genetics ; Humans ; Male ; Models, Statistical ; Molecular Sequence Data ; Point Mutation ; Risk Factors ; *Selection, Genetic ; Viral Load
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-06-06
    Description: The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 10(8) antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved "public epitopes" for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, George J -- Kula, Tomasz -- Xu, Qikai -- Li, Mamie Z -- Vernon, Suzanne D -- Ndung'u, Thumbi -- Ruxrungtham, Kiat -- Sanchez, Jorge -- Brander, Christian -- Chung, Raymond T -- O'Connor, Kevin C -- Walker, Bruce -- Larman, H Benjamin -- Elledge, Stephen J -- AI082630/AI/NIAID NIH HHS/ -- DA033541/DA/NIDA NIH HHS/ -- N01-A1-30024/PHS HHS/ -- N01-AI-30024/AI/NIAID NIH HHS/ -- N01-AL-15422/PHS HHS/ -- R01 DE018925-04/DE/NIDCR NIH HHS/ -- R37AI067073/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):aaa0698. doi: 10.1126/science.aaa0698.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Biophysics, Harvard University, Cambridge, MA 02115, USA. Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA. ; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02115, USA. ; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA. ; Solve ME/CFS Initiative, Los Angeles, CA 90036, USA. ; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, Durban, South Africa. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University, Cambridge, MA 02139, USA. Max Planck Institute for Infection Biology, Chariteplatz, D-10117 Berlin, Germany. ; Vaccine and Cellular Immunology Laboratory, Department of Medicine, Faculty of Medicine; and Chula-Vaccine Research Center, Chulalongkorn University, Bangkok, Thailand. ; Asociacion Civil IMPACTA Salud y Educacion, Lima, Peru. ; AIDS Research Institute-IrsiCaixa and AIDS Unit, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain. ; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA. ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, Durban, South Africa. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University, Cambridge, MA 02139, USA. ; Division of Immunology, Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA. ; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA. Solve ME/CFS Initiative, Los Angeles, CA 90036, USA. selledge@genetics.med.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26045439" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Viral/*blood ; Epitopes, B-Lymphocyte/genetics/*immunology ; High-Throughput Nucleotide Sequencing/methods ; Host-Pathogen Interactions/*immunology ; Humans ; Immune System/*virology ; Immunoprecipitation/methods ; Peptide Library ; Serologic Tests ; Virus Diseases/blood/*diagnosis/immunology ; Viruses/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-12-17
    Description: It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
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