TY - JOUR
T1 - Long-term control of simian immunodeficiency virus (SIV) in cynomolgus macaques not associated with efficient SIV-specific CD8+ T-cell responses
AU - Bruel, Timothée
AU - Hamimi, Chiraz
AU - Dereuddre-Bosquet, Nathalie
AU - Cosma, Antonio
AU - Shin, So Youn
AU - Corneau, Aurélien
AU - Versmisse, Pierre
AU - Karlsson, Ingrid
AU - Malleret, Benoit
AU - Targat, Brice
AU - Barré-Sinoussi, Françoise
AU - Grand, Roger Le
AU - Pancino, Gianfranco
AU - Sáez-Cirión, Asier
AU - Vaslin, Bruno
N1 - Publisher Copyright:
© 2015, American Society for Microbiology.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924807004&partnerID=8YFLogxK
U2 - 10.1128/JVI.03723-14
DO - 10.1128/JVI.03723-14
M3 - Article
C2 - 25589645
AN - SCOPUS:84924807004
SN - 0022-538X
VL - 89
SP - 3542
EP - 3556
JO - Journal of Virology
JF - Journal of Virology
IS - 7
ER -