PMID- 18003729
OWN - NLM
STAT- MEDLINE
DCOM- 20080124
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 82
IP  - 2
DP  - 2008 Jan
TI  - The spike glycoprotein of murine coronavirus MHV-JHM mediates 
      receptor-independent infection and spread in the central nervous systems of 
      Ceacam1a-/- Mice.
PG  - 755-63
AB  - 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.
FAU - Miura, Tanya A
AU  - Miura TA
AD  - Department of Microbiology MS 8333, University of Colorado Health Sciences 
      Center, 12800 E. 19th Ave., P.O. Box 6511, Aurora, CO 80045, USA.
FAU - Travanty, Emily A
AU  - Travanty EA
FAU - Oko, Lauren
AU  - Oko L
FAU - Bielefeldt-Ohmann, Helle
AU  - Bielefeldt-Ohmann H
FAU - Weiss, Susan R
AU  - Weiss SR
FAU - Beauchemin, Nicole
AU  - Beauchemin N
FAU - Holmes, Kathryn V
AU  - Holmes KV
LA  - eng
GR  - N01AI60021/AI/NIAID NIH HHS/United States
GR  - R01 AI025231/AI/NIAID NIH HHS/United States
GR  - AI60021/AI/NIAID NIH HHS/United States
GR  - AI25231/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071114
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Ceacam1 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Virulence Factors)
SB  - IM
MH  - Animals
MH  - Brain/pathology/virology
MH  - Carcinoembryonic Antigen/*genetics
MH  - Central Nervous System/*virology
MH  - Coronavirus Infections/*virology
MH  - Gene Deletion
MH  - Lethal Dose 50
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Murine hepatitis virus/*growth & development/physiology
MH  - Spike Glycoprotein, Coronavirus
MH  - Survival Analysis
MH  - Viral Envelope Proteins/genetics/*physiology
MH  - Virulence Factors/genetics/physiology
MH  - *Virus Internalization
PMC - PMC2224565
EDAT- 2007/11/16 09:00
MHDA- 2008/01/25 09:00
PMCR- 2008/05/01
CRDT- 2007/11/16 09:00
PHST- 2007/11/16 09:00 [pubmed]
PHST- 2008/01/25 09:00 [medline]
PHST- 2007/11/16 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - JVI.01851-07 [pii]
AID - 1851-07 [pii]
AID - 10.1128/JVI.01851-07 [doi]
PST - ppublish
SO  - J Virol. 2008 Jan;82(2):755-63. doi: 10.1128/JVI.01851-07. Epub 2007 Nov 14.