Targeting HIV reservoirs in cells and tissue sanctuaries represents an important issue in HIV research. Follicular helper T cells (Tfh) in lymph nodes (LN) are an important cellular compartment for viral persistence. Remarkably, African green monkeys (AGMs) do not progress towards disease, despite high viremia and CD4+ T cell depletion in the intestinal mucosae. Our previous studies indicate that Tfh cells are not resistant to SIVagm infection in AGMs and reveal a crucial role for NK cells in the viral control within LNs of AGMs. NK cells express CD94/NKG2 which is the receptor of MHC-E. MHC-E binds peptides that derive from the leader sequence of other MHC-I molecules but can also bind viral peptides in the context of infection that can activate or inhibit NK cell activity via the recognition by NKG2 receptors. Nonamer peptides derived from the Env leader sequence of HIV-1 and SIV were able to bind to MHC-E. Moreover, Tfh cells express high levels of MHC-E AND MHC-E+ Tfh cell frequencies decreased in SIVagm-infected AGMs but not in SIVmac-infected MACs. Previous results from the team indicated that NK cells from uninfected AGMs and MACs displayed a stronger MHC-E dependent suppressor activity in the presence of the SIVagm peptide than in the presence of the SIVmac peptide in vitro, indicating that the SIVmac peptide strongly inhibited the MHC-E dependent NK cell lytic activity in contrast to the SIVagm peptide. To understand the impact of MHC-E-peptide/NK cell receptors interaction on NK cell activity and viral control in HIV/SIV infections in vivo, we proposed to analyze this activity in the non-human primate model. We infected MACs with a recombinant SIVmac239 clone coding for the SIVagm.sab92018 nonamer in the ENV leader sequence. As control, we infected MACs with the Wt infectious molecular SIVmac239 clone. This study should help to better understand the role of NK cells in HIV/SIV infection and the mechanism of how they control a tissue viral reservoir.
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