title: Specific mutation of a gammaherpesvirus-expressed antigen in response to CD8 T cell selection in vivo.
abstract: Herpesviruses are thought to be highly genetically stable, and their use as vaccine vectors has been proposed. However, studies of the human gammaherpesvirus, Epstein-Barr virus, have found viral isolates containing mutations in HLA class I-restricted epitopes. Using murine gammaherpesvirus 68 expressing ovalbumin (OVA), we examined the stability of a gammaherpesvirus antigenic locus under strong CD8 T cell selection in vivo. OVA-specific CD8 T cells selected viral isolates containing mutations in the OVA locus but minimal alterations in other genomic regions. Thus, a CD8 T cell response to a gammaherpesvirus-expressed antigen that is not essential for replication or pathogenesis can result in selective mutation of that antigen in vivo. This finding may have relevance for the use of herpesvirus vectors for chronic antigen expression in vivo.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Loh
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Popkin
authors.forename: Lindsay
authors.initials: L
authors.lastname: Droit
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Braaten
authors.forename: Guoyan
authors.initials: G
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Punit
authors.initials: P
authors.lastname: Vachharajani
authors.forename: Nancy
authors.initials: N
authors.lastname: Myers
authors.forename: Ted H
authors.initials: TH
authors.lastname: Hansen
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D057131:Immune Evasion; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010047:Ovalbumin / Q000235:genetics* / Q000276:immunology; D018144:Rhadinovirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
chemical_list: D010047:Ovalbumin