The protease-sensitive loop of the vesicular stomatitis virus matrix protein is involved in virus assembly and protein translation

• Published in: Virology (New York, N.Y.) N.Y.), 2011-07, Vol.416 (1), p.16-25
• Main Authors: Mire, Chad E, Whitt, Michael A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cell Line; Cricetinae; Gene Expression Regulation, Viral - physiology; Infectious Disease; Matrix protein; Models, Molecular; Mutation; Peptide Hydrolases - metabolism; Protein Biosynthesis; Protein Conformation; Vesicular stomatitis virus; Vesiculovirus - genetics; Vesiculovirus - metabolism; Viral Matrix Proteins - genetics; Viral Matrix Proteins - metabolism; Virus assembly; Virus Assembly - physiology; Virus protein translation
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2011.04.013

Abstract To study the contribution of the protease-sensitive loop of the VSV M protein in virus assembly we recovered recombinant VSV (rVSV) with mutations in this region and examined virus replication. Mutations in the highly conserved LXD motif (aa 123–125) resulted in reduced virion budding, reduced virus titers and enhanced M protein exchange with M-ribonucleocapsid complexes (M-RNPs), suggesting that the mutant M proteins were less tightly associated with RNP skeletons . In addition, viral protein synthesis began to decrease at 4 h post-infection (hpi) and was reduced by ~ 80% at 8 hpi for the mutant rVSV-D125A. The reduced protein synthesis was not due to decreased VSV replication or transcription; however, translation of a reporter gene with an EMCV IRES was not reduced, suggesting that cap-dependent, but not cap-independent translation initiation was affected in rVSV-D125A infected cells. These results indicate that the LXD motif is involved in both virus assembly and VSV protein translation.