Journal
JOURNAL OF VIROLOGY
Volume 77, Issue 23, Pages 12572-12578Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.77.23.12572-12578.2003
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007387, R01AI020729, R37AI020729] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI20729, T32 AI007387, R01 AI020729, R37 AI020729] Funding Source: Medline
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Virus-specific cytotoxic T lymphocytes (CTL) exert intense selection pressure on replicating simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in infected individuals. The immunodominantMamu-A*01-restricted Gag p11C, C-M epitope is highly conserved among all sequenced isolates of SIV and therefore likely is structurally constrained. The strategies used by virus isolates to mutate away from an immunodominant epitope-specific CTL response are not well defined. Here we demonstrate that the emergence of a position 2 p11C, C-M epitope substitution (T47I) in a simian-human immunodeficiency virus (SHIV) strain 89.6P-infected Mamu-A*01(+) monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (171V) of the capsid protein. An analysis of the SIV and HIV-2 sequences from the Los Alamos HIV Sequence Database revealed a significant association between any position 2 p11C, GM epitope mutation and the I71V mutation. The T47I mutation alone is associated with significant decreases in viral protein expression, infectivity, and replication, and these deficiencies are restored to wild-type levels with the introduction of the flanking I71V mutation. Together, these data suggest that a compensatory mutation is selected for in SHIN strain 89.61P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope.
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