Sequence analysis of the S gene of recombinant MHV-2/A59 coronaviruses reveals three candidate mutations associated with demyelination and hepatitis

• Published in: Journal of neurovirology Vol. 7; no. 5; pp. 432 - 436
• Main Author: Das Sarma, Li Fu, Susan T. Hingley, Michael M. C. Lai, Ehud Lavi, Jayasri
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01-10-2001; Springer-Verlag
• Subjects: Amino Acid Substitution; Animals; AS gene; Brain - pathology; Brain - virology; Cardiovirus Infections - pathology; Cardiovirus Infections - virology; Coronavirus; Demyelinating Diseases - pathology; Demyelinating Diseases - virology; Encephalitis, Viral - pathology; Encephalitis, Viral - virology; Genes, Viral; Hepatitis, Viral, Animal - pathology; Hepatitis, Viral, Animal - virology; Liver - pathology; Liver - virology; Male; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Meningitis, Viral - pathology; Meningitis, Viral - virology; Mice; Mice, Inbred C57BL; Murine hepatitis virus; Murine hepatitis virus - classification; Murine hepatitis virus - genetics; Murine hepatitis virus - pathogenicity; Murine hepatitis virus - physiology; Point Mutation; Recombination, Genetic; S gene; Sequence Analysis, RNA; Species Specificity; Spike Glycoprotein, Coronavirus; Spinal Cord - pathology; Spinal Cord - virology; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - physiology; Viral Structural Proteins - genetics; Virulence - genetics
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1080/135502801753170282

Coronaviruses, mouse hepatitis virus (MHV) strains, exhibit various degrees of neurotropism and hepatotropism following intracerebral (IC) infection of 4-week-old C57Bl/6 mice. Whereas MHV-A59 produces acute meningitis, encephalitis, hepatitis, and chronic demyelination, a closely related strain, MHV-2, produces only acute meningitis and hepatitis. We previously reported that the spike glycoprotein gene of MHV contains determinants of demyelination and hepatitis. To further investigate the site of demyelination and hepatitis determinants within the S gene, we sequenced the S gene of several nondemyelinating recombinant viruses. We found that three encephalitis-positive, demyelination-negative, hepatitis-negative recombinant viruses have an MHV-A59-derived S gene, which contains three identical point mutations (I375M, L652I, and T1087N). One or more of the sites of these mutations in the MHV-A59 genome are likely to contribute to demyelination and hepatitis.