title: CD8+ T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in vivo, and many revert after transmission.
abstract: Virus-specific CD8(+) T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr., Madison, WI 53711, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Mudd
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ericsen
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Walsh
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: León
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maness
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014779:Virus Replication
chemical_list: D015395:Histocompatibility Antigens Class I