Simian-human immunodeficiency virus escape from cytotoxic T-lymphocyte recognition at a structurally constrained epitope
| Autor: | Heidi S. Bazick, Fred W. Peyerl, Dan H. Barouch, Kevin J. Kunstman, Jennifer Kunstman, Wendy W. Yeh, Norman L. Letvin, Steven M. Wolinsky |
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| Rok vydání: | 2003 |
| Předmět: |
Viral protein
Protein Conformation viruses Immunology Molecular Sequence Data Gene Products gag Biology medicine.disease_cause Microbiology Epitope Virus Cell Line Epitopes Virology medicine Cytotoxic T cell Animals Humans Point Mutation Amino Acid Sequence Prospective Studies DNA Primers Genetics Base Sequence Sequence Homology Amino Acid Point mutation virus diseases HIV Haplorhini Simian immunodeficiency virus Genes gag CTL Capsid Insect Science Pathogenesis and Immunity Simian Immunodeficiency Virus T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of virology. 77(23) |
| ISSN: | 0022-538X |
| Popis: | 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 immunodominant Mamu-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-infectedMamu-A*01+monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (I71V) 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, C-M 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 SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope. |
| Databáze: | OpenAIRE |
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