This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Publicover, J. Articles by Rose, J. K. Search for Related Content PubMed PubMed Citation Articles by Publicover, J. Articles by Rose, J. K.

 Previous Article  |  Next Article 

Journal of Virology, July 2006, p. 7028-7036, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00478-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rapid Pathogenesis Induced by a Vesicular Stomatitis Virus Matrix Protein Mutant: Viral Pathogenesis Is Linked to Induction of Tumor Necrosis Factor Alpha

Jean Publicover,^1,2 Elizabeth Ramsburg,^2, Michael Robek,² and John K. Rose^2*

Section of Microbial Pathogenesis,¹ Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510²

Received 7 March 2006/ Accepted 27 April 2006

Vesicular stomatitis virus (VSV) matrix (M) protein blocks host mRNA export from the nucleus and thereby inhibits interferon induction in infected cells. M mutants with mutations of methionine 51 (M51) lack this shutoff function. We examined pathogenesis of a VSV M mutant with a deletion of M51 (VSVM51) after intranasal infection of BALB/c mice and found an unexpected phenotype. Mice that received VSVM51 experienced a more rapid but overall less severe weight loss than mice that received the recombinant wild-type VSV (rwtVSV). Rapid weight loss was not explained by faster initial replication because VSVM51 replication was controlled faster than rwtVSV replication in the lungs and did not spread systemically like rwtVSV. This faster control of VSVM51 correlated with a more rapid induction of interferon in the lung. Because tumor necrosis factor alpha (TNF-) is associated with weight loss, we examined TNF- induction in mice infected with rwtVSV or VSVM51. We found more-rapid induction of TNF- by the mutant at early times after infection, while rwtVSV induced more TNF- later in infection. This result suggested that TNF- induction might explain both the rapid weight loss caused by the mutant and the overall greater weight loss caused by the rwtVSV. Using TNF- knockout mice (C57BL/6 background), we showed that weight loss following rwtVSV infection was greatly reduced in the absence of TNF-. Although the rapid weight loss caused by VSVM51 was less pronounced in C57BL/6 mice, it was eliminated in the absence of TNF-. These results indicate a role for TNF- in the pathogenesis of VSV.

Present address: Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710.

This article has been cited by other articles:

• Ahmed, M., Marino, T. R., Puckett, S., Kock, N. D., Lyles, D. S. (2008). Immune Response in the Absence of Neurovirulence in Mice Infected with M Protein Mutant Vesicular Stomatitis Virus. J. Virol. 82: 9273-9277 [Abstract] [Full Text]  
• Irie, T., Carnero, E., Okumura, A., Garcia-Sastre, A., Harty, R. N. (2007). Modifications of the PSAP region of the matrix protein lead to attenuation of vesicular stomatitis virus in vitro and in vivo. J. Gen. Virol. 88: 2559-2567 [Abstract] [Full Text]