Effects of Amino Acid Insertions in the Cysteine-Rich Domain of the MHV-A59 Spike Protein on Cell Fusion
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 494)
The spike protein is a key determinant in the pathogenesis of mouse hepatitis virus strain A59 (Hingley et al., 1994). The spike is a type I viral envelope glycoprotein that mediates receptor-binding and viral entry through virus-cell fusion. In addition, when present on the cell surface, the spike can also mediate cell-cell fusion between infected and neighboring cells. During maturation, the spike protein is post-translationally cleaved into two 90 kDa subunits, S1 and S2. Unlike other viral fusion proteins, fusion mediated by the spike protein does not require a cleavage step that liberates a fusion peptide on the N-terminus of the membrane bound subunit (Bos et al., 1997; Bos et al, 1995; Gombold et al., 1993). Instead, a portion of heptad repeat 1 has been suggested to serve as an internal fusion peptide (Luo and Weiss, 1998a; Luo and Weiss, 1998b). In the current model of fusion, fusion peptides are proposed to mediate lipid mixing between the outer leaflets of the viral envelope and cell membrane. This leads to an intermediate stage, termed hemifusion, in which the inner leaflets remain intact. Resolution of hemifusion is thought to be mediated by the transmembrane anchor. Among coronaviruses, there is significant sequence conservation within the spike transmembrane anchor and cysteine-rich (cys) domain. Both the transmembrane anchor and the cys domain of the spike protein have been shown to be necessary for cell-cell fusion activity (Bos et al., 1995; Chang et al., 2000). In this report, we examine how changes in the length of the transmembrane anchor and the consequent change in spacing of the cys domain affect cell fusion activity.
KeywordsFusion Activity Spike Protein Amino Acid Insertion Viral Fusion Protein Transmembrane Anchor
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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