Long-term control of simian immunodeficiency virus (SIV) in cynomolgus macaques not associated with efficient SIV-specific CD8+ T-cell responses

Timothée Bruel, Chiraz Hamimi, Nathalie Dereuddre-Bosquet, Antonio Cosma, So Youn Shin, Aurélien Corneau, Pierre Versmisse, Ingrid Karlsson, Benoit Malleret, Brice Targat, Françoise Barré-Sinoussi, Roger Le Grand, Gianfranco Pancino, Asier Sáez-Cirión, Bruno Vaslin*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

The spontaneous control of human and simian immunodeficiency viruses (HIV/SIV) is typically associated with specific major histocompatibility complex (MHC) class I alleles and efficient CD8+ T-cell responses, but many controllers maintain viral control despite a nonprotective MHC background and weak CD8+ T-cell responses. Therefore, the contribution of this response to maintaining long-term viral control remains unclear. To address this question, we transiently depleted CD8+ T cells from five SIV-infected cynomolgus macaques with long-term viral control and weak CD8+ T-cell responses. Among them, only one carried the protective MHC allele H6. After depletion, four of five controllers experienced a transient rebound of viremia. The return to undetectable viremia was accompanied by only modest expansion of SIV-specific CD8+ T cells that lacked efficient SIV suppression capacity ex vivo. In contrast, the depletion was associated with homeostatic activation/expansion of CD4+ T cells that correlated with viral rebound. In one macaque, viremia remained undetectable despite efficient CD8+ cell depletion and inducible SIV replication from its CD4+ T cells in vitro. Altogether, our results suggest that CD8+ T cells are not unique contributors to the long-term maintenance of low viremia in this SIV controller model and that other mechanisms, such as weak viral reservoirs or control of activation, may be important players in control.

Original languageEnglish
Pages (from-to)3542-3556
Number of pages15
JournalJournal of Virology
Volume89
Issue number7
DOIs
Publication statusPublished - 2015
Externally publishedYes

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