Journal
JOURNAL OF VIROLOGY
Volume 81, Issue 2, Pages 503-513Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01218-06
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Funding
- NIAID NIH HHS [R01-AI21572] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI021572] Funding Source: NIH RePORTER
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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) poIR mutants may be due to enhanced production of double-stranded RNA (dsRNA). We show here that poIR 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 poIR 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 poIR 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 poIR growth. Both key aspects of poIR 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 poIR 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.
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