Journal
JOURNAL OF VIROLOGY
Volume 78, Issue 5, Pages 2581-2585Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.78.5.2581-2585.2004
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Funding
- NCRR NIH HHS [5 P51 RR001676-43] Funding Source: Medline
- NIAID NIH HHS [R01-AI-46366, R01 AI046366, R01 AI049120, R01-AI-49120] Funding Source: Medline
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Selection for escape mutant immunodeficiency viruses by cytotoxic T lymphocytes (CTL) has been well characterized and may be associated with disease progression. CTL epitopes accrue escape mutations at different rates in vivo. Interestingly, certain high-frequency CTL do not select for escape until the chronic phase of infection. Here we show that mutations conferring escape from immunodominant CTL directed against an epitope in the viral Gag protein are strongly associated with extraepitopic mutations in gag in vivo. The extraepitopic mutations partially restore in vitro replicative fitness of viruses bearing the escape mutations. Constraints on epitope sequences may therefore play a role in determining the rate of escape from CTL responses in vivo.
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