+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Pathogenesis of chimeric MHV4/MHV-A59 recombinant viruses: the murine coronavirus spike protein is a major determinant of neurovirulence

Pathogenesis of chimeric MHV4/MHV-A59 recombinant viruses: the murine coronavirus spike protein is a major determinant of neurovirulence

Journal of Virology 73(9): 7752-7760

The mouse hepatitis virus (MHV) spike glycoprotein, S, has been implicated as a major determinant of viral pathogenesis. In the absence of a full-length molecular clone, however, it has been difficult to address the role of individual viral genes in pathogenesis. By using targeted RNA recombination to introduce the S gene of MHV4, a highly neurovirulent strain, into the genome of MHV-A59, a mildly neurovirulent strain, we have been able to directly address the role of the S gene in neurovirulence. In cell culture, the recombinants containing the MHV4 S gene, S4R22 and S4R21, exhibited a small-plaque phenotype and replicated to low levels, similar to wild-type MHV4. Intracranial inoculation of C57BL/6 mice with S4R22 and S4R21 revealed a marked alteration in pathogenesis. Relative to wild-type control recombinant viruses (wtR13 and wtR9), containing the MHV-A59 S gene, the MHV4 S gene recombinants exhibited a dramatic increase in virulence and an increase in both viral antigen staining and inflammation in the central nervous system. There was not, however, an increase in the level of viral replication in the brain. These studies demonstrate that the MHV4 S gene alone is sufficient to confer a highly neurovirulent phenotype to a recombinant virus deriving the remainder of its genome from a mildly neurovirulent virus, MHV-A59. This definitively confirms previous findings, suggesting that the spike is a major determinant of pathogenesis.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 011121058

Download citation: RISBibTeXText

PMID: 10438865

Related references

In vitro properties and pathogenesis of A59/MHV4 chimeric mouse hepatitis viruses. Advances in Experimental Medicine and Biology 494: 169-172, 2001

Both spike and background genes contribute to murine coronavirus neurovirulence. Journal of Virology 80(14): 6834-6843, 2006

Multiple regions of the murine coronavirus spike glycoprotein influence neurovirulence. Journal of Neurovirology 7(5): 421-431, 2001

Localization of neurovirulence determinant for rats on the S1 subunit of murine coronavirus JHMV. Virology 208(1): 67-74, 1995

Characterization and development of recombinant vaccinia viruses expressing different segments of spike protein derived from human coronavirus NL-63. Bing du Xue Bao 27(3): 250-256, 2011

Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein. Virology 239(1): 1-10, 1997

The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: definition of critical epitopes by variant analysis. Journal of General Virology 69: 87-98, 1988

The N-terminal region of the murine coronavirus spike glycoprotein is associated with the extended host range of viruses from persistently infected murine cells. Journal of Virology 78(17): 9073-9083, 2004

Targeted recombination within the spike gene of murine coronavirus mouse hepatitis virus-A59: Q159 is a determinant of hepatotropism. Journal of Virology 72(12): 9628-9636, 1998

Recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism. Journal of Virology 77(16): 9084-9089, 2003

Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus. Journal of Virology 87(15): 8638-8650, 2013

The function of the coronavirus spike protein in viral pathogenesis. Journal of Cellular Biochemistry Suppl. (12 Part C): 38, 1988

Roles of spike protein in the pathogenesis of SARS coronavirus. Hong Kong Medical Journal 15(Suppl. 2): 37-40, 2009

SARS coronavirus spike polypeptide DNA vaccine priming with recombinant spike polypeptide from Escherichia coli as booster induces high titer of neutralizing antibody against SARS coronavirus. Vaccine 23(42): 4959-4968, 2005

Calreticulin as a hydrophilic chimeric molecular adjuvant enhances IgG responses to the spike protein of severe acute respiratory syndrome coronavirus. Microbiology and Immunology 56(8): 554-561, 2012