|Irie, Takashi -|
|Liu, Yuliang -|
|Carnero, Elena -|
|Garcia-Sastre, Adolfo -|
|Harty, Ronald -|
Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 12, 2012
Publication Date: September 19, 2012
Repository URL: http://www.mdpi.com/1999-4915/4/9/1605
Citation: Irie, T., Liu, Y., Drolet, B.S., Carnero, E., Garcia-Sastre, A., Harty, R.N. 2012. Cytopathogenesis of Vesicular Stomatitis virus is regulated by the PSAP motif of M protein in a species-dependent manner. Viruses. 4: 1605-1618. Interpretive Summary: Vesicular stomatitis virus (VSV) is an insect transmitted virus that causes disease in cattle, horses and swine. The matrix (M) protein is believed to play several important roles in the ability of the virus to cause disease. When a specific region of M was genetically altered, the virus multiplied much less efficiently and caused significantly less disease in mice. Interestingly, this virus multiplied more efficiently in insect cells and caused much more cell death than is typical. These findings suggest that this specific region of the M protein of VSV plays an important role in how well virus grows and how much disease it is able to cause in different species.
Technical Abstract: 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 the Aedes albopictus C6/36 mosquito cell line. 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 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 a cell line 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.