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.
Original language | English (US) |
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Pages (from-to) | 34-48 |
Number of pages | 15 |
Journal | Virology |
Volume | 450-451 |
DOIs | |
State | Published - Feb 2014 |
Externally published | Yes |
Keywords
- Autologous viral variants
- CART
- HIV-1
- Memory T cell responses
- Primary T cell responses
ASJC Scopus subject areas
- Virology