Conversion of nonfusing mumps virus infections to fusing infections by selective proteolysis of the HN glycoprotein.
Mumps virus strains differ in their ability to induce cell fusion following an infection: strains with active neuraminidase (NANase) fail to cause cell fusion, while strains with less active NANase cause cell fusion. When chymotrypsin is added to infected cells, cell fusion is amplified in a concentration-dependent manner for all mumps virus strains. Virions produced in such infections do not express HN glycoprotein-associated activities. Chymotrypsin treatment of purified mumps virus in vitro results in sequential cleavage of the HN glycoprotein without affecting F glycoprotein structure. Initially, HN is cleaved into two glycopolypeptides, HNc1 (32K) and HNc2' (41K), with concomitant loss of hemagglutinating and NANase activities, and infectivity. Further incubation with chymotrypsin causes complete degradation of HNc1 and digestion of HNc2' to HNc2 (13K-19K). Both HNc2' and HNc2 contain the [3H]palmitic acid label found in the HN polypeptide, which suggests that these fragments are associated with the viral membrane. Analyses of infected cells and released virions indicate that chymotrypsin acts similarly on HN exposed at the cell surface. Exogenous NANase does not abolish the protease-augmented cell fusion, though it does reduce cell fusion of untreated fusing strain infections. These results confirm that mumps virus HN glycoprotein is critically linked to cell fusion cytopathology and show that cryptic cell fusion activity in nonfusing strain infections can be unmasked by the proteolytic removal of the HN glycoprotein.
D000818:Animals; D002459:Cell Fusion / Q000187:drug effects; D002918:Chymotrypsin / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism*; D015707:HN Protein; D006801:Humans; D009107:Mumps / Q000382:microbiology*; D009109:Mumps virus / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D009439:Neuraminidase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000494:pharmacology*; D014764:Viral Proteins / Q000378:metabolism*; D014776:Virus Cultivation
D006023:Glycoproteins; D015707:HN Protein; D014764:Viral Proteins; D009439:Neuraminidase; D010447:Peptide Hydrolases; D002918:Chymotrypsin