+ 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

Murine coronavirus spike glycoprotein mediates degree of viral spread, inflammation, and virus-induced immunopathology in the central nervous system



Murine coronavirus spike glycoprotein mediates degree of viral spread, inflammation, and virus-induced immunopathology in the central nervous system



Virology 301(1): 9-20



The mouse hepatitis virus (MHV) spike glycoprotein is a major determinant of neurovirulence. We investigated how alterations in spike affect neurovirulence using two isogenic recombinant viruses differing exclusively in spike. S4R, containing the MHV-4 spike gene, is dramatically more neurovirulent than SA59R, containing the MHV-A59 spike gene (J. J. Phillips, M. M. Chua, E. Lavi, and S. R. Weiss, 1999, J. Virol. 73, 7752-7760). We examined the contribution of differences in cellular tropism, viral spread, and the immune response to infection to the differential neurovirulence of S4R and SA59R. MHV-4 spike-mediated neurovirulence was associated with extensive viral spread in the brain in both neurons and astrocytes. Infection of primary hippocampal neuron cultures demonstrated that S4R spread more rapidly than SA59R and suggested that spread may occur between cells in close physical contact. In addition, S4R infection induced a massive influx of lymphocytes into the brain, a higher percentage of CD8+ T cells, and a higher frequency of MHV-specific CD8+ T cells relative SA59R infection. Despite this robust and viral-specific immune response to S4R infection, infection of RAG1-/- mice suggested that immune-mediated pathology also contributes to the high neurovirulence of S4R.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 009916883

Download citation: RISBibTeXText

PMID: 12359451

DOI: 10.1006/viro.2002.1551


Related references

The spike glycoprotein of murine coronavirus MHV-JHM mediates receptor-independent infection and spread in the central nervous systems of Ceacam1a-/- Mice. Journal of Virology 82(2): 755-763, 2008

Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system. Virology 312(2): 9-80, 2003

Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System. Plos Pathogens 11(11): E1005261, 2015

Murine coronavirus receptors are differentially expressed in the central nervous system and play virus strain-dependent roles in neuronal spread. Journal of Virology 84(21): 11030-11044, 2010

Effects of an epitope-specific CD8+ T-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants. Journal of Virology 78(3): 1150-1159, 2004

TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. Journal of Virology 93(6):, 2019

The role of mast cells in virus-induced inflammation in the murine central nervous system. Cellular Immunology 86(2): 491-500, 1984

Conformational Changes in the Spike Glycoprotein of Murine Coronavirus Are Induced at 37C either by Soluble Murine Ceacam1 Receptors or by pH 8. Journal of Virology 77(2): 830-840, 2003

Enhanced green fluorescent protein expression may be used to monitor murine coronavirus spread in vitro and in the mouse central nervous system. Journal of Neurovirology 8(5): 381-391, 2002

Conformational changes in the spike glycoprotein of murine coronavirus are induced at 37 degrees C either by soluble murine CEACAM1 receptors or by pH 8. Journal of Virology 77(2): 830-840, 2003

Increased viral titers and enhanced reactivity of antibodies to the spike glycoprotein of murine coronavirus produced by infection at pH 6. Journal Of Virological Methods. 50(1-3): 237-244, 1994

Fibrin deposition in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease. Journal of Neuroimmunology 77(2): 185-194, 1997

Regional localization of virus in the central nervous system of mice persistently infected with murine coronavirus JHM. Virology 166(2): 328-338, 1988

The N-terminal domain of the murine coronavirus spike glycoprotein determines the CEACAM1 receptor specificity of the virus strain. Journal of Virology 77(2): 841-850, 2003

The N-Terminal Domain of the Murine Coronavirus Spike Glycoprotein Determines the Ceacam1 Receptor Specificity of the Virus Strain. Journal of Virology 77(2): 841-850, 2003