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Journal of Virology, January 2007, p. 503-513, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01218-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Overproduction of Double-Stranded RNA in Vesicular Stomatitis Virus-Infected Cells Activates a Constitutive Cell-Type-Specific Antiviral Response{triangledown}

Derek Ostertag,{dagger} Traci M. Hoblitzell-Ostertag,{ddagger} and Jacques Perrault*

Department of Biology and Center for Microbial Sciences, San Diego State University, San Diego, California 92182

Received 10 June 2006/ Accepted 11 October 2006

In a companion paper (D. Ostertag, T. M. Hoblitzell-Ostertag, and J. Perrault, J. Virol. 81:492-502, 2007), we provided indirect evidence that cell-type-specific growth restriction of the vesicular stomatitis virus (VSV) polR mutants may be due to enhanced production of double-stranded RNA (dsRNA). We show here that polR growth in mouse L-929 cells was rescued by vaccinia virus coinfection and that sole expression of the vaccinia virus dsRNA-binding E3L protein, via coinfection with an engineered VSV minigenome, also restored polR growth. Expression of dsRNA-binding protein NS1A or NS1B from influenza virus, but not C protein from Sendai virus, which does not bind dsRNA, likewise effected polR rescue. The N-terminal dsRNA-binding domain of NS1A, only 73 amino acids in length, but not a full-size mutant NS1A lacking dsRNA-binding activity, restored polR growth. Both key aspects of polR growth restriction, namely inhibition of genome replication and release of low-infectivity virus particles, were countered by expression of the dsRNA-binding proteins. We tested the effects of overproducing dsRNA in wild-type VSV infections by coinfecting cells with a VSV recombinant expressing the sense strand of the enhanced green fluorescent protein gene (VSV-GFP) and one expressing the antisense strand (VSV-PFG). These coinfections mimicked all aspects of polR restriction, including host range, lack of effect on transcription, reduced virus particle infectivity, and insensitivity to inhibition of host gene transcription or dsRNA-activated protein kinase activity. We conclude that, for some cell types, overproduction of dsRNA during VSV infection triggers an immediate and constitutive host cell antiviral effector response independent of interferon induction or signaling.

* Corresponding author. Mailing address: Department of Biology, NLS 401, San Diego State University, 5500 Campanile Drive, San Diego, CA 91182. Phone and fax: (619) 594-5676. E-mail: jperrault{at}sunstroke.sdsu.edu.

{triangledown} Published ahead of print on 25 October 2006.

{dagger} Present address: The Burnham Institute for Medical Research, La Jolla, CA 92037.

{ddagger} Present address: Ligand Pharmaceuticals, San Diego, CA 92121.

Journal of Virology, January 2007, p. 503-513, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01218-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Takeuchi, K., Komatsu, T., Kitagawa, Y., Sada, K., Gotoh, B. (2008). Sendai Virus C Protein Plays a Role in Restricting PKR Activation by Limiting the Generation of Intracellular Double-Stranded RNA. J. Virol. 82: 10102-10110 [Abstract] [Full Text]  
  • Strahle, L., Marq, J.-B., Brini, A., Hausmann, S., Kolakofsky, D., Garcin, D. (2007). Activation of the Beta Interferon Promoter by Unnatural Sendai Virus Infection Requires RIG-I and Is Inhibited by Viral C Proteins. J. Virol. 81: 12227-12237 [Abstract] [Full Text]  
  • Ostertag, D., Hoblitzell-Ostertag, T. M., Perrault, J. (2007). Cell-Type-Specific Growth Restriction of Vesicular Stomatitis Virus polR Mutants Is Linked to Defective Viral Polymerase Function. J. Virol. 81: 492-502 [Abstract] [Full Text]  


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