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Protection against CTL escape and clinical disease in a murine model of virus persistence
Journal article   Peer reviewed

Protection against CTL escape and clinical disease in a murine model of virus persistence

Taeg S Kim and Stanley Perlman
Journal of immunology (Baltimore, Md. : 1950), Vol.171(4), pp.2006-2013
08/15/2003
DOI: 10.4049/jimmunol.171.4.2006
PMID: 12902505

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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.
Recombinant Fusion Proteins - immunology Humans Epitopes, T-Lymphocyte - genetics Vaccines, Synthetic - immunology Gene Deletion Encephalomyelitis - prevention & control Viral Proteins - administration & dosage Peptide Fragments - genetics Disease Models, Animal Vaccines, Synthetic - chemistry Viral Proteins - analysis Glycoproteins - genetics Amino Acid Sequence Epitopes, T-Lymphocyte - analysis Vaccines, Synthetic - biosynthesis Viral Proteins - genetics Coronavirus Infections - immunology Peptide Fragments - biosynthesis Glycoproteins - administration & dosage Peptide Fragments - analysis T-Lymphocytes, Cytotoxic - metabolism Lymphocytic choriomeningitis virus - genetics Mice Mice, Inbred BALB C HeLa Cells Chronic Disease Murine hepatitis virus - genetics Coronavirus Infections - prevention & control Lymphocytic choriomeningitis virus - immunology Encephalomyelitis - genetics Encephalomyelitis - virology Epitopes, T-Lymphocyte - biosynthesis Antigens, Viral - administration & dosage Molecular Sequence Data Antigens, Viral - genetics Epitopes, T-Lymphocyte - administration & dosage Murine hepatitis virus - immunology Female Antigens, Viral - biosynthesis Viral Proteins - biosynthesis Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - biosynthesis T-Lymphocytes, Cytotoxic - immunology Antigens, Viral - analysis T-Lymphocytes, Cytotoxic - virology Mice, Inbred C57BL Peptide Fragments - administration & dosage Coronavirus Infections - genetics Recombinant Fusion Proteins - chemical synthesis Glycoproteins - biosynthesis Animals Encephalomyelitis - immunology Glycoproteins - analysis Vaccines, Synthetic - administration & dosage Virus Latency - immunology Virus Latency - genetics

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