HIV-1-Specific CD4+ T-Cell Responses Are Not Associated With Significant Viral Epitope Variation in Persons With Persistent Plasma Viremia

Abstract

To determine whether increased sequence variation occurs in regions of endogenous HIV-1 targeted by HIV-1-specific CD4 T cells. The presence of increased variation would be suggestive of immune evasion by HIV-1. We performed a cross-sectional study of untreated HIV-1-infected subjects measuring HIV-1-specific interferon (IFN)-gamma-secreting CD4 T-cell responses against epitopes in Gag p17 and p24 and concurrent endogenous plasma HIV-1 RNA epitope sequence variation. CD8- depleted IFNgamma enzyme-linked immunospot assays were used to identify regions of HIV-1 Gag recognized by CD4 T cells. Reverse transcriptase polymerase chain reaction and TA cloning were used to sequence endogenous plasma HIV-1 virus and identify variants. CD4 T-cell epitopes in Gag p17 and p24 were identified in 5 individuals, and concurrent sequence information on endogenous HIV-1 was obtained in 4 of these individuals. Endogenous plasma HIV-1 RNA sequencing revealed no intrapatient amino acid sequence variation through identified epitopes. In these chronically infected viremic subjects, circulating IFNgamma-secreting CD4 T-cell responses were directed against epitope sequences found in the predominant strain of endogenous circulating plasma HIV-1, suggesting that escape from CD4 T-cell responses is not a common process in vivo.