title: The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8⁺ T cell responses.
abstract: It is unclear if HIV-1 variants lose the ability to prime naïve CD8(+) cytotoxic T lymphocytes (CTL) during progressive, untreated infection. We conducted a comprehensive longitudinal analysis of viral evolution and its impact on primary and memory CD8(+) T cell responses pre-seroconversion (SC), post-SC, and during combination antiretroviral therapy (cART). Memory T cell responses targeting autologous virus variants reached a nadir by 8 years post-SC with development of AIDS, followed by a transient enhancement of anti-HIV-1 CTL responses upon initiation of cART. We show broad and high magnitude primary T cell responses to late variants in pre-SC T cells, comparable to primary anti-HIV-1 responses induced in T cells from uninfected persons. Despite evolutionary changes, CD8(+) T cells could still be primed to HIV-1 variants. Hence, vaccination against late, mutated epitopes could be successful in enhancing primary reactivity of T cells for control of the residual reservoir of HIV-1 during cART.
authors: American University of Beirut, Faculty of Health Sciences, Medical Laboratory Sciences Program, 11-0236 Riad El Solh, 1107-2020 Beirut, Lebanon.
authors: Nada M
authors: NM
authors: Melhem
authors: University of Pittsburgh, School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA 15213, USA.
authors: Kellie N
authors: KN
authors: Smith
authors: University of Pittsburgh, Graduate School of Public Health, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, 15261, USA.
authors: Xiao-Li
authors: XL
authors: Huang
authors: Pennsylvania State University, M.S. Hershey Medical Center College of Medicine, Department of Public Health Sciences, Hershey, PA 17033, USA.
authors: Bonnie A
authors: BA
authors: Colleton
authors: University of Pittsburgh, Graduate School of Public Health, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, 15261, USA.
authors: Weimin
authors: W
authors: Jiang
authors: University of Pittsburgh, Graduate School of Public Health, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, 15261, USA.
authors: Robbie B
authors: RB
authors: Mailliard
authors: University of Washington, School of Medicine, Department of Microbiology, Seattle, WA 98195-8070, USA.
authors: James I
authors: JI
authors: Mullins
authors: University of Pittsburgh, Graduate School of Public Health, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, 15261, USA. Electronic address: rinaldo@pitt.edu.
authors: Charles R
authors: CR
authors: Rinaldo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins
keywords: Autologous viral variants; HIV-1; Memory T cell responses; Primary T cell responses; cART