Back to Search
Start Over
The spike glycoprotein of murine coronavirus MHV-JHM mediates receptor-independent infection and spread in the central nervous systems of Ceacam1a-/- Mice.
- Source :
-
Journal of virology [J Virol] 2008 Jan; Vol. 82 (2), pp. 755-63. Date of Electronic Publication: 2007 Nov 14. - Publication Year :
- 2008
-
Abstract
- The MHV-JHM strain of the murine coronavirus mouse hepatitis virus is much more neurovirulent than the MHV-A59 strain, although both strains use murine CEACAM1a (mCEACAM1a) as the receptor to infect murine cells. We previously showed that Ceacam1a(-/-) mice are completely resistant to MHV-A59 infection (E. Hemmila et al., J. Virol. 78:10156-10165, 2004). In vitro, MHV-JHM, but not MHV-A59, can spread from infected murine cells to cells that lack mCEACAM1a, a phenomenon called receptor-independent spread. To determine whether MHV-JHM could infect and spread in the brain independent of mCEACAM1a, we inoculated Ceacam1a(-/-) mice. Although Ceacam1a(-/-) mice were completely resistant to i.c. inoculation with 10(6) PFU of recombinant wild-type MHV-A59 (RA59) virus, these mice were killed by recombinant MHV-JHM (RJHM) and a chimeric virus containing the spike of MHV-JHM in the MHV-A59 genome (SJHM/RA59). Immunohistochemistry showed that RJHM and SJHM/RA59 infected all neural cell types and induced severe microgliosis in both Ceacam1a(-/-) and wild-type mice. For RJHM, the 50% lethal dose (LD(50)) is <10(1.3) in wild-type mice and 10(3.1) in Ceacam1a(-/-) mice. For SJHM/RA59, the LD(50) is <10(1.3) in wild-type mice and 10(3.6) in Ceacam1a(-/-) mice. This study shows that infection and spread of MHV-JHM in the brain are dependent upon the viral spike glycoprotein. RJHM can initiate infection in the brains of Ceacam1a(-/-) mice, but expression of mCEACAM1a increases susceptibility to infection. The spread of infection in the brain is mCEACAM1a independent. Thus, the ability of the MHV-JHM spike to mediate mCEACAM1a-independent spread in the brain is likely an important factor in the severe neurovirulence of MHV-JHM in wild-type mice.
- Subjects :
- Animals
Brain pathology
Brain virology
Gene Deletion
Lethal Dose 50
Membrane Glycoproteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Murine hepatitis virus physiology
Spike Glycoprotein, Coronavirus
Survival Analysis
Viral Envelope Proteins genetics
Virulence Factors genetics
Virulence Factors physiology
Carcinoembryonic Antigen genetics
Central Nervous System virology
Coronavirus Infections virology
Membrane Glycoproteins physiology
Murine hepatitis virus growth & development
Viral Envelope Proteins physiology
Virus Internalization
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 82
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 18003729
- Full Text :
- https://doi.org/10.1128/JVI.01851-07