Protection against CTL escape and clinical disease in a murine model of virus persistence.
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.
Kim
Taeg S
TS
Interdisciplinary Program in Immunology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
Perlman
Stanley
S
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*
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