دورية أكاديمية
أعرض في EDS

Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection.

التفاصيل البيبلوغرافية
العنوان: Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection.
المؤلفون: Macharia GN; Department of Medicine, Imperial College London, London, United Kingdom.; IAVI Human Immunology Laboratory, London, United Kingdom., Yue L; Emory Vaccine Centre, Yerkes National Primate Research Centre, Emory University, Atlanta, GA, United States of America., Staller E; Department of Medicine, Imperial College London, London, United Kingdom.; IAVI Human Immunology Laboratory, London, United Kingdom., Dilernia D; Emory Vaccine Centre, Yerkes National Primate Research Centre, Emory University, Atlanta, GA, United States of America., Wilkins D; Emory Vaccine Centre, Yerkes National Primate Research Centre, Emory University, Atlanta, GA, United States of America., Song H; Emory Vaccine Centre, Yerkes National Primate Research Centre, Emory University, Atlanta, GA, United States of America., McGowan E; Department of Medicine, Imperial College London, London, United Kingdom.; IAVI Human Immunology Laboratory, London, United Kingdom., King D; Department of Medicine, Imperial College London, London, United Kingdom.; IAVI Human Immunology Laboratory, London, United Kingdom., Fast P; IAVI, New York, NY, United States of America., Imami N; Department of Medicine, Imperial College London, London, United Kingdom., Price MA; IAVI, New York, NY, United States of America.; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, United States of America., Sanders EJ; Kenya Medical Research Institute-Wellcome Trust, Kilifi, Kenya.; Nuffield Department of Clinical Medicine, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington, United Kingdom., Hunter E; Emory Vaccine Centre, Yerkes National Primate Research Centre, Emory University, Atlanta, GA, United States of America.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States of America., Gilmour J; Department of Medicine, Imperial College London, London, United Kingdom.; IAVI Human Immunology Laboratory, London, United Kingdom.
المصدر: PLoS pathogens [PLoS Pathog] 2020 Sep 04; Vol. 16 (9), pp. e1008853. Date of Electronic Publication: 2020 Sep 04 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Founder Effect* , HIV Infections*/genetics , HIV Infections*/immunology , HIV Infections*/pathology , Virus Replication*/genetics , Virus Replication*/immunology , gag Gene Products, Human Immunodeficiency Virus*/genetics , gag Gene Products, Human Immunodeficiency Virus*/immunology, CD4-Positive T-Lymphocytes/*immunology , HIV-1/*physiology, Acute Disease ; Adolescent ; Adult ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/virology ; Female ; Humans ; Male ; Middle Aged ; Viremia/genetics ; Viremia/immunology ; Viremia/pathology
مستخلص: HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants' samples was sequenced close to transmission (median 21 days post infection, IQR 18-41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to probe effective immune responses against TF.
Competing Interests: The authors have declared that no competing interests exist.
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; P51 OD011132 United States OD NIH HHS; R01 AI124968 United States AI NIAID NIH HHS; 107752/Z/15/Z United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (gag Gene Products, Human Immunodeficiency Virus)
تواريخ الأحداث: Date Created: 20200904 Date Completed: 20201013 Latest Revision: 20240429
رمز التحديث: 20240429
مُعرف محوري في PubMed: PMC7498102
DOI: 10.1371/journal.ppat.1008853
PMID: 32886726
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1008853