633. HIV-1 Vpu Immune Correlates in a Narrow-Source Infection Cohort: Impact of ADCC and KIR-Associated Pressure

Abstract

BackgroundWe investigated vpu diversity and immune correlates of sequence variation in a unique cohort of former plasma donors (FPDs) from rural China who were infected with a very narrow range of clade B’ HIV-1 strains.MethodsPlasma viral RNA was sequenced from a convenience sample of 90 SM cohort samples, and then analyzed for polymorphisms associated with HLA class I and KIR genotypes. An ADCC assay was employed to detect responses to Env and Vpu peptides. An ELISA-based approach was optimized to identify potential Vpu epitopes. Finally, responders from the ADCC assay were assessed in an ADCVI assay.ResultsIn keeping with lack of CTL targeting, no HLA class I associated polymorphisms were identified in Vpu. KIR analysis, however revealed evidence of a strong association between KIR2DS1 and a single amino acid at position 14 of Vpu. 59% of HIV-1 sequences derived from KIR2DS1+ individuals encoded a valine (V) at this position whereas the consensus amino acid alanine (A) was found at this position in the majority (76%) of KIR2DS1-individuals. ADCC responses to Env were found in 37% of the SM cohort, with only five subjects also showing responses to Vpu peptides. Plasma from all five Env/vpu responders showed potent inhibition of virus replication, nearing 95%, in the ADCVI assay.ConclusionWe demonstrate a significant association between an activating KIR, KIR2DS1, and a polymorphism at amino acid position 14 of HIV-1 Vpu, which is consistent with selection by Natural Killer (NK) cells expressing this KIR. We also demonstrate Vpu and Env ADCC responses that are associated with potent virus inhibition in vitro in responders. These data help to shed light upon the immune selection pressures exerted on the HIV-1 vpu gene and may provide insights into the role of this protein in immune evasion.Disclosures All authors: No reported disclosures.