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Cytopathogenesis of Vesicular Stomatitis Virus is Regulated by the PSAP Motif of M Protein in a Species-Dependent Manner

Irie, Takashi, Liu, Yuliang, Drolet, Barbara S., Carnero, Elena, Garcia-Sastre, Adolfo, Harty, Ronald N.
Viruses 2012 v.4 pp. 1605
Aedes albopictus, Culicoides sonorensis, Vesiculovirus, alanine, apoptosis, brain, caspases, cattle, cytopathogenicity, enzyme activity, horses, host-pathogen relationships, hosts, insect vectors, insects, lungs, mice, mortality, mutation, notifiable disease, pathogens, phenotype, viral proteins, viruses, weight loss
Vesicular stomatitis virus (VSV) is an important vector-borne pathogen of bovine and equine species, causing a reportable vesicular disease. The matrix (M) protein of VSV is multifunctional and plays a key role in cytopathogenesis, apoptosis, host protein shut-off, and virion assembly/budding. Our previous findings indicated that mutations of residues flanking the 37PSAP40 motif within the M protein resulted in VSV recombinants having attenuated phenotypes in mice. In this report, we characterize the phenotype of VSV recombinant PS > A4 (which harbors four alanines (AAAA) in place of the PSAP motif without disruption of flanking residues) in both mice, and in Aedes albopictus C6/36 mosquito and Culicoides sonorensis KC cell lines. The PS > A4 recombinant displayed an attenuated phenotype in infected mice as judged by weight loss, mortality, and viral titers measured from lung and brain samples of infected animals. However, unexpectedly, the PS > A4 recombinant displayed a robust cytopathic phenotype in insect C6/36 cells compared to that observed with control viruses. Notably, titers of recombinant PS > A4 were approximately 10-fold greater than those of control viruses in infected C6/36 cells and in KC cells from Culicoides sonorensis, a known VSV vector species. In addition, recombinant PS > A4 induced a 25-fold increase in the level of C3 caspase activity in infected C6/36 cells. These findings indicate that the PSAP motif plays a direct role in regulating cytopathogenicity in a species-dependent manner, and suggest that the intact PSAP motif may be important for maintaining persistence of VSV in an insect host.