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  • The EMBO Journal (2003) 22, 5655 - 5665
  • doi:10.1093/emboj/cdg562

Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus

Olaf Isken1,2, Claus W. Grassmann1, Robert T. Sarisky3, Michael Kann1, Suisheng Zhang4, Frank Grosse4, Peter N. Kao5 and Sven-Erik Behrens1,2

  1. Institute for Virology, Justus-Liebig-Universität Giessen, Frankfurter Stras zlige 107, D-35392 Giessen, Germany
  2. Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
  3. Department of Virology, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road UP1450, Collegeville, PA 19426, USA
  4. Institute of Molecular Biotechnology, Department of Biochemistry, Beutenbergstras zlige 11, D-07745 Jena, Germany
  5. Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA 94305, USA

Correspondence to:

Sven-Erik Behrens, E-mail: SE_Behrens@fccc.edu

Received 14 May 2003; Accepted 12 September 2003; Revised 20 August 2003

A major issue of current virology concerns the characterization of cellular proteins that operate as functional components of the viral multiplication process. Here we describe a group of host factors designated as 'NFAR proteins' that are recruited by the replication machinery of bovine viral diarrhea virus, a close relative of the human pathogen hepatitis C virus. The NFAR proteins associate specifically with both the termini of the viral RNA genome involving regulatory elements in the 5' and 3' non-translated regions. Modification of the protein interaction sites in the 3' non-translated region yielded viral RNAs that were replication deficient. Viral replication was also inhibited by RNAi approaches that reduced the concentration of RNA helicase A, a member of the NFAR group, in the host cell's cytoplasm. Further experimental data suggest that NFAR proteins mediate a circular conformation of the viral genome that may be important for the coordination of translation and replication. Because NFAR proteins are presumed components of the antiviral response, we suspect that viral recruitment may also serve to weaken cellular defense mechanisms.

  • Keywords:

    • hepatitis C virus,
    • NF90,
    • NFAR,
    • pestivirus,
    • RNA helicase A