Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects

Abstract

Background: The purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution. Results: Fifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma. Gag and Nef proteins were the main targets of CTL responses during the first year of HIV-1 infection, and this was evident from the data after adjusting for the length of amino acids by dividing the amino acids number of the corresponding protein and multiplying by 100. Additionally, relative magnitudes of Gag at both 3 months and 1 year post infection were significantly negatively correlated with the viral set point (p=0.002, r=-0.726; p=0.025, r=-0.574). While the relative magnitude of Nef at 1 year post infection were significantly positively correlated with viral set point (p=0.004, r=0.697). Subjects with multi-layered Gag immunodominant responses during the first year of infection had significantly lower viral set points than subjects without such responses (p=0.002). Conclusion: Multi-layered Gag immunodominant responses during the first year of infection were correlated with viral control, which provides a theoretical basis for vaccine design targeting MSM subjects with the CRF01_AE subtype.