Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication.

ABSTRACT: Human leukocyte antigen (HLA)-B27-positive subjects are uncommon in their ability to control infection with human immunodeficiency virus type 1 (HIV-1). However, late viral escape from a narrowly directed immunodominant Gag-specific CD8(+) T-lymphocyte (CTL) response has been linked to AIDS progression in these individuals. Identifying the mechanism of the immune-mediated control may provide critical insights into HIV-1 vaccine development. Here, we illustrate that the CTL escape mutation R(264)K in the HLA-B27-restricted KK10 epitope in the capsid resulted in a significant defect in viral replication in vitro. The R(264)K variant was impaired in generating late reverse transcription products, indicating that replication was blocked at a postentry step. Notably, the R(264)K mutation was as

SUBMITTER: Schneidewind A 

PROVIDER: S-EPMC2169010 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature