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Journal of Virology, August 2008, p. 7977-7987, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.02762-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cellular La Protein Shields Nonsegmented Negative-Strand RNA Viral Leader RNA from RIG-I and Enhances Virus Growth by Diverse Mechanisms{triangledown}

Vira Bitko,1 Alla Musiyenko,1 Mark A. Bayfield,2 Richard J. Maraia,2 and Sailen Barik1*

Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, 307 University Blvd., Mobile, Alabama 36688-0002,1 Intramural Research Program on Genetics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, 31 Center Drive, Bethesda, Maryland 208922

Received 19 December 2007/ Accepted 29 May 2008

The La antigen (SS-B) associates with a wide variety of cellular and viral RNAs to affect gene expression in multiple systems. We show that La is the major cellular protein found to be associated with the abundant 44-nucleotide viral leader RNA (leRNA) early after infection with respiratory syncytial virus (RSV), a nonsegmented negative-strand RNA virus. Consistent with this, La redistributes from the nucleus to the cytoplasm in RSV-infected cells. Upon RNA interference knockdown of La, leRNA is redirected to associate with the RNA-binding protein RIG-I, a known activator of interferon (IFN) gene expression, and this is accompanied by the early induction of IFN mRNA. These results suggest that La shields leRNA from RIG-I, abrogating the early viral activation of type I IFN. We mapped the leRNA binding function to RNA recognition motif 1 of La and showed that while wild-type La greatly enhanced RSV growth, a La mutant defective in RSV leRNA binding also did not support RSV growth. Comparative studies of RSV and Sendai virus and the use of IFN-negative Vero cells indicated that La supports the growth of nonsegmented negative-strand RNA viruses by both IFN suppression and a potentially novel IFN-independent mechanism.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, 307 University Blvd., Mobile, AL 36688-0002. Phone: (251) 460-6860. Fax: (251) 460-6850. E-mail: sbarik{at}jaguar1.usouthal.edu

{triangledown} Published ahead of print on 11 June 2008.

Journal of Virology, August 2008, p. 7977-7987, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.02762-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Swedan, S., Musiyenko, A., Barik, S. (2009). Respiratory Syncytial Virus Nonstructural Proteins Decrease Levels of Multiple Members of the Cellular Interferon Pathways. J. Virol. 83: 9682-9693 [Abstract] [Full Text]  
  • Manuse, M. J., Parks, G. D. (2009). Role for the Paramyxovirus Genomic Promoter in Limiting Host Cell Antiviral Responses and Cell Killing. J. Virol. 83: 9057-9067 [Abstract] [Full Text]  
  • Bousquet-Antonelli, C., Deragon, J.-M. (2009). A comprehensive analysis of the La-motif protein superfamily. RNA 15: 750-764 [Abstract] [Full Text]  


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