Rapid Viral Escape at an Immunodominant Simian-Human Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitope Exacts a Dramatic Fitness Cost

摘要: Escape from specific T-cell responses contributes to the progression of human immunodeficiency virus type 1 (HIV-1) infection. escape viral variants are retained following HIV-1 transmission between major histocompatibility complex (MHC)-matched individuals. However, reversion wild can occur MHC-mismatched hosts in absence cytotoxic T-lymphocyte (CTL) pressure, due reduced fitness mutant virus. We estimated both strength immune selection and cost by studying rates pigtail macaques. Near-complete replacement wild-type with at an immunodominant simian Gag epitope KP9 occurred rapidly (over 7 days) infection macaques SHIVSF162P3. Another challenge virus, SHIVmn229, previously serially passaged through macaques, contained a mutation 40/44 clones sequenced stock. When six KP9-responding animals were infected this was maintained. By contrast, not responding KP9, rapid K165R over 2 weeks after The rapidity sequence suggests significant mutant. Quantifying pressure exerted CTL costs has important implications for development CTL-based vaccine strategies.