The virulence of mouse hepatitis virus strain A59 is not dependent on efficient spike protein cleavage and cell-to-cell fusion.
The cleavage and fusion properties of recombinant murine hepatitis viruses (MHV) were examined to assess the role of the cleavage signal in determining the extent of S protein cleavage, and the correlation between cleavage and induction of cell-to-cell fusion. Targeted recombination was used to introduce amino acid substitutions into the cleavage signal of the fusion glycoprotein (spike or S protein) of MHV strain A59. The recombinants were then used to address the question of the importance of S protein cleavage and viral-mediated cell-to-cell fusion on pathogenicity. Our data indicate that cleavage of spike is not solely determined by the amino acid sequence at the cleavage site, but may also depend on sequences removed from the cleavage site. In addition, efficient cell-to-cell fusion is not necessary for virulence.
Hingley
Susan T
ST
Department of Pathology, Microbiology and Immunology, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania 19131, USA. susanh@pcom.edu
Leparc-Goffart
Isabelle
I
Seo
Su-Hun
SH
Tsai
Jean C
JC
Weiss
Susan R
SR
D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000821:virology; D002494:Central Nervous System Infections / Q000821:virology*; D018352:Coronavirus Infections / Q000821:virology*; D004195:Disease Models, Animal; D015726:Giant Cells / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics / Q000472:pathogenicity*; D011995:Recombination, Genetic; D064370:Spike Glycoprotein, Coronavirus; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D014774:Virulence
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus