Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus.
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.
Institute for Virology, Justus-Liebig-Universität Giessen, Frankfurter Strasse 107, D-35392 Giessen, Germany.
Olaf
O
Isken
Claus W
CW
Grassmann
Robert T
RT
Sarisky
Michael
M
Kann
Suisheng
S
Zhang
Frank
F
Grosse
Peter N
PN
Kao
Sven-Erik
SE
Behrens
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D050779:Nuclear Factor 90 Proteins; D009690:Nucleic Acid Conformation; D010750:Phosphoproteins; D034622:RNA Interference; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000302:isolation & purification / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology
D020413:3' Untranslated Regions; C429643:ILF3 protein, human; D050779:Nuclear Factor 90 Proteins; D010750:Phosphoproteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins