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Koeppe, J.R. et al.

Koeppe, Campbell, Rapaport, Wilson,

HIV-1-specific CD4+ T-cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia.

OBJECTIVES: 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. DESIGN: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.[1]

References

HIV-1-specific CD4+ T-cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia. Koeppe, J.R., Campbell, T.B., Rapaport, E.L., Wilson, C.C. J. Acquir. Immune Defic. Syndr. (2006) [Pubmed]

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