title: Protection against CTL escape and clinical disease in a murine model of virus persistence.
abstract: CTL escape mutations have been identified in several chronic infections, including mice infected with mouse hepatitis virus strain JHM. One outstanding question in understanding CTL escape is whether a CD8 T cell response to two or more immunodominant CTL epitopes would prevent CTL escape. Although CTL escape at multiple epitopes seems intuitively unlikely, CTL escape at multiple CD8 T cell epitopes has been documented in some chronically infected individual animals. To resolve this apparent contradiction, we engineered a recombinant variant of JHM that expressed the well-characterized gp33 epitope of lymphocytic choriomeningitis virus, an epitope with high functional avidity. The results show that the presence of a host response to this second epitope protected mice against CTL escape at the immunodominant JHM-specific CD8 T cell epitope, the persistence of infectious virus, and the development of clinical disease.
authors.affiliation: Interdisciplinary Program in Immunology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Taeg S
authors.initials: TS
authors.lastname: Kim
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D002908:Chronic Disease; D018352:Coronavirus Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006023:Glycoproteins / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D017735:Virus Latency / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus