Next Article in Journal
Potential Vaccines and Post-Exposure Treatments for Filovirus Infections
Next Article in Special Issue
Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry
Previous Article in Journal
Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa
Viruses 2012, 4(9), 1605-1618; doi:10.3390/v4091605
Article

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

1,†
, 2,†
, 3
, 4
, 5,6,7,
 and 2,*
1 Department of Virology, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan 2 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104, USA 3 Arthropod-Borne Animal Diseases Research Unit, United States Department of Agriculture, Agricultural Research Service, 1515 College Ave., Manhattan, KS 66502, USA 4 Department of Hepatology and Gene Therapy, University of Navarra, E-31009 Pamplona, Spain 5 Department of Microbiology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA 6 Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA 7 Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 10 August 2012 / Revised: 11 September 2012 / Accepted: 12 September 2012 / Published: 19 September 2012
(This article belongs to the Special Issue Recent Findings on the Biology of Rhabdovirus)
View Full-Text   |   Download PDF [1872 KB, uploaded 19 September 2012]   |   Browse Figures

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 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.
Keywords: vesicular stomatitis virus, VSV recombinant; M protein; apoptosis; cytopathic; CPE; insect; persistence; motif vesicular stomatitis virus, VSV recombinant; M protein; apoptosis; cytopathic; CPE; insect; persistence; motif
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

Irie, T.; Liu, Y.; Drolet, B.S.; Carnero, E.; García-Sastre, A.; Harty, R.N. Cytopathogenesis of Vesicular Stomatitis Virus Is Regulated by the PSAP Motif of M Protein in a Species-Dependent Manner. Viruses 2012, 4, 1605-1618.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert