Strong SIV-specific memory NK cell responses formed in acute infection persist during chronic SIV infection 3354

Abstract Description Natural killer (NK) cells provide rapid and robust innate responses against viral infections. Multiple studies have shown that NK cells also mount antigen-specific recall responses. In nonhuman primates (NHP), antigen-specific memory-like NK cells are largely defined by MHC-E-dependent responses. However, the full mechanisms underlying the response remains unclear. We identified SIV peptide-dependent NK cell responses during the SIV-acute phase via intracellular staining. To investigate antigen-specific memory NK cells, we developed an NK cell clonal in vitro method (rhNKCL) and applied it to rhesus macaques (RM). During SIV infection, NK cells exhibited increased CD107a in PBMCs and Ki67 in spleen tissues in response to SIV-derived peptides. Furthermore, there were significantly higher rhNKCL responses to one SIV ENV-derived MHC-E-restricted peptide in SIV-chronic compared to SIV-naïve RM. Moreover, rhNKCL from SIV-chronic infected RM showed significant upregulation of tissue-retention markers (CD49a+CD69+) and downregulation of FcepsilonRIgamma/Syk markers, characteristic of an adaptive NK cell profile. Our findings demonstrate that select SIV-derived peptides can elicit NK cell responses in SIV-acute infection and reveal an antigen-specific memory NK cell profile in the chronic phase in response to SIV-derived peptides. These data highlight the importance of investigating antiviral NK cell activity in future vaccine strategies and NK cell therapies. Funding Sources Supported by NIH R01A035464; R01AI161010; Duke CFAR P30 AI064518 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)