PMID- 10438865
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 73
IP  - 9
DP  - 1999 Sep
TI  - Pathogenesis of chimeric MHV4/MHV-A59 recombinant viruses: the murine coronavirus 
      spike protein is a major determinant of neurovirulence.
PG  - 7752-60
AB  - 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.
FAU - Phillips, J J
AU  - Phillips JJ
AD  - Departments of Microbiology, University of Pennsylvania School of Medicine, 
      Philadelphia, Pennsylvania 19104-6076, USA.
FAU - Chua, M M
AU  - Chua MM
FAU - Lavi, E
AU  - Lavi E
FAU - Weiss, S R
AU  - Weiss SR
LA  - eng
GR  - P01 NS030606/NS/NINDS NIH HHS/United States
GR  - NS-21954/NS/NINDS NIH HHS/United States
GR  - T32 GM007229/GM/NIGMS NIH HHS/United States
GR  - NS-30606/NS/NINDS NIH HHS/United States
GR  - GM-07229/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Viral)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
MH  - Animals
MH  - Antigens, Viral/metabolism
MH  - Brain/pathology/*virology
MH  - Cell Line
MH  - Coronavirus Infections/pathology/*virology
MH  - Liver/virology
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Murine hepatitis virus/genetics/growth & development/*pathogenicity/physiology
MH  - Reassortant Viruses/pathogenicity
MH  - Spike Glycoprotein, Coronavirus
MH  - Viral Envelope Proteins/genetics/*physiology
MH  - Virulence
MH  - Virus Replication
PMC - PMC104302
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
PMCR- 1999/09/01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
PHST- 1999/09/01 00:00 [pmc-release]
AID - 0547 [pii]
AID - 10.1128/JVI.73.9.7752-7760.1999 [doi]
PST - ppublish
SO  - J Virol. 1999 Sep;73(9):7752-60. doi: 10.1128/JVI.73.9.7752-7760.1999.