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Journal of Virology, March 2004, p. 2581-2585, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2581-2585.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Extraepitopic Compensatory Substitutions Partially Restore Fitness to Simian Immunodeficiency Virus Variants That Escape from an Immunodominant Cytotoxic-T-Lymphocyte Response

Wisconsin National Primate Research Center, Madison, Wisconsin 53715,¹ Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, Wisconsin 53706,² Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208³

Received 15 July 2003/ Accepted 7 November 2003

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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