Disease progression despite protective HLA expression in an HIV-infected transmission pair

• DOI: 10.1186/s12977-015-0179-z
• Publication Date: 2015-06-29T07:23:54Z
• Authors: Jacqui Brener; Astrid Gall; Rebecca Batorsky; Lynn Riddell; Soren Buus; Ellen Leitman; Paul Kellam; Todd Allen; Philip Goulder; Philippa C Matthews
• Keywords: Viremia; HLA-B; HLA-B Antigens

The precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear. We studied a CRF01_AE clade infected donor-recipient transmission pair in which the recipient expressed both HLA-B*57:01. Within 4.5 years of diagnosis, had progressed to meet criteria for antiretroviral therapy initiation. employed ultra-deep sequencing full-length virus genome donor an unbiased approach identify specific viral mutations selected association with progression. Using heat map method highlight differences sequences between recipient, we demonstrated majority recipient's outside Env were within epitopes restricted HLA-B*57:01, including well-studied Gag epitopes. donor, who also alleles associated protection, HLA-A*32:01/B*13:02/B*14:01, showed selection parallel these protective alleles. These studies pair, whom but nevertheless failed control viremia, are consistent previous reports pointing critical role Gag-specific CD8+ T cell maintaining infection. subtype infection may have contributed accelerated this result clade-specific sequence immunodominant