title: Cytopathogenesis of vesicular stomatitis virus is regulated by the PSAP motif of M protein in a species-dependent manner.
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 (37)PSAP(40) 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.
authors.affiliation: Department of Virology, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. tirie@hiroshima-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Irie
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Liu
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Drolet
authors.forename: Elena
authors.initials: E
authors.lastname: Carnero
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Harty
mesh_terms: D000330:Aedes; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000821:virology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018353:Rhabdoviridae Infections / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D018116:Vesiculovirus / Q000472:pathogenicity*; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: C094460:M protein, Vesicular stomatitis virus; D014763:Viral Matrix Proteins; D037521:Virulence Factors