This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Korom, M.
Right arrow Articles by Morrison, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Korom, M.
Right arrow Articles by Morrison, L. A.

 Previous Article  |  Next Article 

Journal of Virology, April 2008, p. 3642-3653, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02409-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Selective Ablation of Virion Host Shutoff Protein RNase Activity Attenuates Herpes Simplex Virus 2 in Mice{triangledown}

Maria Korom, Kristine M. Wylie, and Lynda A. Morrison*

Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, Missouri 63104

Received 7 November 2007/ Accepted 16 January 2008

The virion host shutoff (vhs) protein of herpes simplex virus (HSV) has endoribonuclease activity and rapidly reduces protein synthesis in infected cells through mRNA degradation. Herpes simplex virus 1 (HSV-1) and HSV-2 vhs mutants are highly attenuated in vivo, but replication and virulence are largely restored to HSV-2 vhs mutants in the absence of a type I interferon (IFN) response. The role of vhs in pathogenesis and the hindrance of the type I IFN response have classically been examined with viruses that completely lack vhs or express a truncated vhs protein. To determine whether RNase activity is the principal mechanism of vhs-mediated type I IFN resistance and virulence, we constructed a HSV-2 point mutant that synthesizes full-length vhs protein lacking RNase activity (RNase– virus). Wild-type and mutant HSV-2 vhs proteins coimmunoprecipitated with VP16 and VP22. vhs protein bearing the point mutation was packaged into the virion as efficiently as the wild-type vhs protein. Like a mutant encoding truncated vhs, the RNase– virus showed IFN-dependent replication that was restricted compared with that of the wild-type virus. The RNase– virus was highly attenuated in wild-type mice infected intravaginally, with reduced mucosal replication, disease severity, and spread to the nervous system comparable to those of the vhs truncation mutant. Surprisingly, in alpha/beta interferon (IFN-{alpha}/β) receptor knockout mice, the vhs RNase mutant was more attenuated than the vhs truncation mutant in terms of disease severity and virus titer in vaginal swabs and central nervous system samples, suggesting that non-enzymatically active vhs protein interferes with efficient virus replication. Our results indicate that vhs enzymatic activity plays a complex role in vhs-mediated type I IFN resistance during HSV-2 infection.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, Missouri 63104. Phone: (314) 977-8874. Fax: (314) 977-8717. E-mail: morrisla{at}slu.edu

{triangledown} Published ahead of print on 30 January 2008.

Journal of Virology, April 2008, p. 3642-3653, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02409-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»