JVI Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lin, Y.
Right arrow Articles by He, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, Y.
Right arrow Articles by He, B.

 Previous Article  |  Next Article 

Journal of Virology, March 2003, p. 3371-3383, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3371-3383.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Induction of Apoptosis by Paramyxovirus Simian Virus 5 Lacking a Small Hydrophobic Gene

Yuan Lin,1 Angela C. Bright,1,2 Terri A. Rothermel,1 and Biao He1,2*

Department of Veterinary Science,1 Graduate Program in Immunobiology in the Life Science Consortium, Pennsylvania State University, University Park, Pennsylvania 168022

Received 18 August 2002/ Accepted 19 December 2002

Simian virus 5 (SV5) is a member of the paramyxovirus family, which includes emerging viruses such as Hendra virus and Nipah virus as well as many important human and animal pathogens that have been known for years. SV5 encodes eight known viral proteins, including a small hydrophobic integral membrane protein (SH) of 44 amino acids. SV5 without the SH gene (rSV5{Delta}SH) is viable, and growth of rSV5{Delta}SH in tissue culture cells and viral protein and mRNA production in rSV5{Delta}SH-infected cells are indistinguishable from those of the wild-type SV5 virus. However, rSV5{Delta}SH causes increased cytopathic effect (CPE) and apoptosis in MDBK cells and is attenuated in vivo, suggesting the SH protein plays an important role in SV5 pathogenesis. How rSV5{Delta}SH induces apoptosis in infected cells has been examined in this report. Tumor necrosis factor alpha (TNF-{alpha}), a proinflammatory cytokine, was detected in culture media of rSV5{Delta}SH-infected cells. Apoptosis induced by rSV5{Delta}SH was inhibited by neutralizing antibodies against TNF-{alpha} and TNF-{alpha} receptor 1 (TNF-R1), suggesting that TNF-{alpha} played an essential role in rSV5{Delta}SH-induced apoptosis in a TNF-R1-dependent manner. Examination of important proteins in the TNF-{alpha} signaling pathway showed that p65, a major NF-{kappa}B subunit whose activation can lead to transcription of TNF-{alpha}, was first translocated to the nucleus and was capable of binding to DNA and then was targeted for degradation in rSV5{Delta}SH-infected cells while expression levels of TNF-R1 remained relatively constant. Thus, rSV5{Delta}SH induced cell death by activating TNF-{alpha} expression, possibly through activation of the NF-{kappa}B subunit p65 and then targeting p65 for degradation, leading to apoptosis.

* Corresponding author. Mailing address: Department of Veterinary Science, Pennsylvania State University, 115 Henning Bldg., University Park, PA 16802. Phone: (814) 863-8533. Fax: (814) 863-6140. E-mail: bxh40{at}psu.edu.

Journal of Virology, March 2003, p. 3371-3383, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3371-3383.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Mol. Cell. Biol. Microbiol. Mol. Biol. Rev.
Clin. Vaccine Immunol. ALL ASM JOURNALS

Copyright © 2003 by the American Society for Microbiology. All rights reserved.