Acute-Phase CD8 T Cell Responses That Select for Escape Variants Are Needed to Control Live Attenuated Simian Immunodeficiency Virus

作者：Harris Max; Burns Charles M; Becker Ericka A; Braasch Andrew T; Gostick Emma; Johnson Randall C; Broman Karl W; Price David A; Friedrich Thomas C; O' Connor Shelby L

来源：Journal of Virology, 2013, 87(16): 9353-9364.

DOI：10.1128/JVI.00909-13

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select for sequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escape variants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239 Delta nef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KO Delta nef. Viremia was significantly higher in M3 homozygous MCMs infected with m3KO Delta nef than in either MHC-mismatched MCMs infected with m3KO Delta nef or MCMs infected with SIVmac239 Delta nef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during early m3KO Delta nef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These results provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase of infection are needed to establish viral control in vivo.

• 出版日期2013-8