A conditional-lethal murine coronavirus mutant that fails to incorporate the spike glycoprotein into assembled virions.
The coronavirus spike glycoprotein (S) mediates both the attachment of virus to the host cell receptor and membrane fusion. We describe here the characterization of a temperature-sensitive mutant of the coronavirus mouse hepatitis virus A59 (MHV-A59) having multiple S protein-related defects. The most remarkable of these was that the mutant, designated Albany 18 (Alb18), assembled virions devoid of the S glycoprotein at the nonpermissive temperature. Alb18 also failed to bring about syncytia formation in cells infected at the nonpermissive temperature. Virions of the mutant assembled at the permissive temperature were much more thermolabile than wild type. Moreover, mutant S protein that was incorporated into virions at the permissive temperature showed enhanced pH-dependent thermolability in its ability to bind to the MHV receptor. Alb18 was found to have a single point mutation in S resulting in a change of serine 287 to isoleucine, and it was shown by revertant analysis that this was the lesion responsible for the phenotype of the mutant.
Ricard
C S
CS
Department of Microbiology, Immunology, and Molecular Genetics, Albany Medical College, NY 12208, USA.
Koetzner
C A
CA
Sturman
L S
LS
Masters
P S
PS
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005814:Genes, Viral; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D011991:Receptors, Virus / Q000378:metabolism; D017421:Sequence Analysis; D064370:Spike Glycoprotein, Coronavirus; D013696:Temperature; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019065:Virus Assembly
D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus