A 12-amino acid stretch in the hypervariable region of the spike protein S1 subunit is critical for cell fusion activity of mouse hepatitis virus
Journal
Journal of Biological Chemistry
Journal Volume
274
Journal Issue
37
Pages
26085-26090
Date Issued
1999
Author(s)
Abstract
The spike (S) glycoprotein of mouse hepatitis virus (MHV) plays a major role in the viral pathogenesis. It is often processed into the N-terminal S1 and the C-terminal S2 subunits that were evidently important for binding to cell receptor and inducing cell-cell fusion, respectively. As a consequence of cell-cell fusion, most of the naturally occurring infections of MHV are associated with syncytia formation. So far, only MHV-2 was identified to be fusion-negative. In this study, the S gene of MHV-2 was molecularly cloned, and the nucleotide sequence was determined. The MHV-2 S protein lacks a 12- amino acid stretch in the S1 hypervariable region from amino acid residue 446 to 457 when compared with the fusion-positive strain MHV-JHM. In addition, there are three amino acid substitutions in the S2 subunit, Tyr-1144 to Asp, Glu-1165 to Asp, and Arg-1209 to Lys. The cloned MHV-2 S protein exhibited the fusion-negative property in DBT cells as the intrinsic viral protein. Furthermore, similar to the fusion-positive MHV-JHM strain, proteolytic cleavage activity was detected both in DBT cells infected with the fusion- negative MHV-2 and in the transfected cells that expressed the cloned MHV-2 S protein. Domain swapping experiments demonstrated that the 12-amino acid stretch missing in the MHV-2 S1 subunit, but not the proteolytic cleavage site, was critical for the cell-fusion activity of MHV.
SDGs
Other Subjects
amino acid; protein subunit; virus glycoprotein; amino terminal sequence; animal cell; article; carboxy terminal sequence; cell fusion; controlled study; hepatitis virus; molecular cloning; mouse; nonhuman; nucleotide sequence; priority journal; protein degradation; receptor binding; sequence analysis; Animals; Base Sequence; Cell Fusion; Cell Line; Cloning, Molecular; DNA Primers; Membrane Glycoproteins; Mice; Molecular Sequence Data; Murine hepatitis virus; Sequence Deletion; Viral Envelope Proteins; Animalia; DNA viruses; Murine hepatitis virus
Type
journal article