Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response

• DOI: 10.1371/journal.ppat.1000365
• Publication Date: 2009-04-02T22:19:15Z
• Authors: Ryan M. Troyer; John McNevin; Yi Liu; Shao Chong Zhang; Randall W. Krizan; Awet Abraha; Denis M. Tebit; Hong Zhao; Santiago Avila; Michael A. Lobritz; M. Juliana McElrath; Sylvie Le Gall; James I. Mullins; Eric J. Arts
• Keywords: CTL*

Human lymphocyte antigen (HLA)-restricted CD8+ cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish replication fitness. Here, we assess the fitness impact of emerging in seven gp120 Env p24 Gag coding regions an individual followed longitudinally from time acute HIV-1 infection, as well some these same recognized other HIV-1-infected individuals. Nine dominant appeared five first year whereas all four found two emerged after nearly years infection. These were introduced individually into autologous gene infection then placed a full-length, infectious genome. When competed against virus parental protein, loss was observed with only one nine mutations, had no effect three conferred slight increase In contrast, conferring significantly decreased One particular mutation epitope associated reduced peptide recognition high costs but replaced by fitness-neutral mutation. to alter processing concomitant response. conclusion, significant costs, most neutral, suggesting balance between immunologic replicative costs.