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Characterization of a variant virus from ascitic fluid of subacute granulomatous serositis in interferon-gamma-deficient C57BL/6 mice persistently infected with murine coronavirus strain JHM

Characterization of a variant virus from ascitic fluid of subacute granulomatous serositis in interferon-gamma-deficient C57BL/6 mice persistently infected with murine coronavirus strain JHM

Viral Immunology 23(4): 437-442

Previously, we showed that intraperitoneal infection with murine coronavirus strain JHM (JHMV) established a persistent infection with subacute granulomatous serositis in interferon-gamma-deficient C57BL/6 (B6-GKO) mice. Herein, we characterize a variant virus from B6-GKO mice persistently infected with JHMV. Viruses were isolated from ascites at 25 d post-infection and cloned by limiting dilution on DBT cells; one variant was named 25V16G. To compare pathogenicity in vivo, we inoculated 25V16G and JHMV intraperitoneally into 8- to 12-week-old B6-GKO mice. Whereas nearly all of the B6-GKO mice infected with JHMV survived over 14 d, all of those infected with 25V16G died by 9 d post-infection. Histopathological examination revealed that 25V16G induced acute fulminant hepatitis in B6-GKO mice, whereas JHMV caused severe but focal hepatitis. The virus titer of 25V16G in the liver was 50- and 250-fold higher than that of JHMV at 5 and 7 d post-infection, respectively. However, there was no significant difference in viral growth between 25V16G and JHMV in cell lines cultured in vitro. Nucleotide sequencing of the S gene of 25V16G and JHMV revealed a deletion of 29 amino acids encompassing S(511-539), which covers a major cytotoxic T lymphocyte (CTL) epitope in C57BL/6 mice, and two point mutations resulting in amino acid changes in the S protein of 25V16G. One explanation for the greater pathogenicity of 25V16G is that 25V16G escapes CTL-mediated protection in B6-GKO mice. This experimental model may be used to assess the role of IFN-gamma in viral persistence in vivo.

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Accession: 052030244

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PMID: 20712488

DOI: 10.1089/vim.2010.0008

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