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Long-Term Control of Simian Immunodeficiency Virus (SIV) in Cynomolgus Macaques Not Associated with Efficient SIV-Specific CD8 + T-Cell Responses.

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.
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Submitted on : Monday, December 12, 2016 - 4:54:03 PM
Last modification on : Friday, June 5, 2020 - 4:02:53 AM
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Timothée Bruel, Chiraz Hamimi, Nathalie Dereuddre-Bosquet, Antonio Cosma, So Youn Shin, et al.. Long-Term Control of Simian Immunodeficiency Virus (SIV) in Cynomolgus Macaques Not Associated with Efficient SIV-Specific CD8 + T-Cell Responses.. Journal of Virology, American Society for Microbiology, 2015, 89 (7), pp.3542 - 3556. ⟨10.1128/JVI.03723-14⟩. ⟨pasteur-01414959⟩

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