Document Detail


Pathogenesis of chimeric MHV4/MHV-A59 recombinant viruses: the murine coronavirus spike protein is a major determinant of neurovirulence.
MedLine Citation:
PMID:  10438865     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J J Phillips; M M Chua; E Lavi; S R Weiss
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  73     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-09-07     Completed Date:  1999-09-07     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7752-60     Citation Subset:  IM    
Affiliation:
Departments of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Viral / metabolism
Brain / pathology,  virology*
Cell Line
Coronavirus Infections / pathology,  virology*
Liver / virology
Membrane Glycoproteins / genetics,  physiology*
Mice
Mice, Inbred C57BL
Murine hepatitis virus / genetics,  growth & development,  pathogenicity*,  physiology
Reassortant Viruses / pathogenicity
Viral Envelope Proteins / genetics,  physiology*
Virulence
Virus Replication
Grant Support
ID/Acronym/Agency:
GM-07229/GM/NIGMS NIH HHS; NS-21954/NS/NINDS NIH HHS; NS-30606/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Viral; 0/Membrane Glycoproteins; 0/Viral Envelope Proteins; 107476-75-5/spike glycoprotein, coronavirus
Comments/Corrections

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