| Summary: | 博士 === 國立臺灣大學 === 生化學研究所 === 87 === 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 evident to be important for binding to cell receptor and inducing cell-cell fusion, respectively. As a consequence of cell-cell fusion, most of 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 residues 446 to 457 when compared to 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 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.
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