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Virology. 2014 Feb;450-451:34-48. doi: 10.1016/j.virol.2013.10.015. Epub 2013 Dec 20.

The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8⁺ T cell responses.

Author information

1
American University of Beirut, Faculty of Health Sciences, Medical Laboratory Sciences Program, 11-0236 Riad El Solh, 1107-2020 Beirut, Lebanon.
2
University of Pittsburgh, School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA 15213, USA.
3
University of Pittsburgh, Graduate School of Public Health, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, 15261, USA.
4
Pennsylvania State University, M.S. Hershey Medical Center College of Medicine, Department of Public Health Sciences, Hershey, PA 17033, USA.
5
University of Washington, School of Medicine, Department of Microbiology, Seattle, WA 98195-8070, USA.
6
University of Pittsburgh, Graduate School of Public Health, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, 15261, USA. Electronic address: rinaldo@pitt.edu.

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.

KEYWORDS:

Autologous viral variants; HIV-1; Memory T cell responses; Primary T cell responses; cART

PMID:
24503065
PMCID:
PMC4110927
DOI:
10.1016/j.virol.2013.10.015
[Indexed for MEDLINE]
Free PMC Article
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