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Published on: September 13, 2018
Difference of two new LCMV strains in lethality and viral genome load in tissues
Toshikazu Takagi1,2, Makiko Ohsawa3, Hitoki Yamanaka3
1Division of Comparative Medicine, Center for Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, Nagasaki 852-8523, Japan.
Abstract:
More than 30 strains of lymphocytic choriomeningitis virus (LCMV) have been isolated from mice, hamsters and humans in the United States, Europe and Japan. Experimentally infected mice exhibit different clinical signs and lethality depending on a combination of LCMV epitope peptides and host major histocompatibility complex (MHC) class I molecules. This study examined the pathogenicity, clinical signs and lethality, of two new LCMV strains (BRC and OQ28) using three inbred mouse strains with different genetic backgrounds having different H-2D haplotypes. Strain OQ28 (OQ28) infected mice exhibited clinical signs and lethality, whereas strain BRC (BRC) infected mice showed no clinical signs of infection. The viral genome load in tissues of C57BL/6 mice infected with two strains was determined using one-step real time RT-PCR. In C57BL/6 mice, higher levels of OQ28 viral genome load were detected in all tissues rather than were present in BRC infected mice. The viral genome load in lungs of both virus strains remained higher levels than in other tissues at 28 days post infection. Comparing sequences of the three LCMV epitope peptide regions revealed one non-conservative amino acid substitution codon in OQ28 and two amino acid differences in BRC. These results suggest that the varied pathogenicity and viral genome load of LCMV strains are not based only on differences in the host MHC class I molecule.
Insights
Two new lymphocytic choriomeningitis virus (LCMV) strains showed varied pathogenicity in mice. Viral genome load and specific viral sequences, not just host genetics, influence LCMV disease.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Lymphocytic choriomeningitis virus (LCMV) strains vary in pathogenicity.
- Host genetics, specifically major histocompatibility complex (MHC) class I molecules, influence LCMV disease outcomes.
Purpose of the Study:
- To investigate the pathogenicity, clinical signs, and lethality of two novel LCMV strains (BRC and OQ28).
- To analyze viral genome load and sequence variations in relation to host genetic background.
Main Methods:
- Infection of three inbred mouse strains with different H-2D haplotypes using LCMV strains BRC and OQ28.
- Assessment of clinical signs and lethality.
- Quantification of viral genome load using real-time RT-PCR.
- Sequence comparison of LCMV epitope peptide regions.
Main Results:
- LCMV strain OQ28 caused clinical signs and lethality, while strain BRC did not.
- C57BL/6 mice infected with OQ28 showed higher viral genome loads in all tissues compared to BRC.
- Viral genome load remained highest in lungs at 28 days post-infection for both strains.
- Sequence analysis revealed distinct amino acid differences in epitope regions between OQ28 and BRC.
Conclusions:
- LCMV strain pathogenicity and viral genome load are influenced by factors beyond host MHC class I molecules.
- Specific viral sequence variations contribute to differential pathogenicity observed between LCMV strains.
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