Nuclear factor NF45 interacts with viral proteins of infectious bursal disease virus and inhibits viral replication.
Two of the central issues in developing new strategies to interfere with viral infections concern the identification of cellular proteins involved in viral replication and/or antiviral measures and the dissection of the underlying molecular mechanisms. To gain initial insight into the role of host proteins in the life cycle of infectious bursal disease virus (IBDV), a double-stranded RNA virus, we examined the cellular nuclear factor 45 (NF45). NF45 was previously indicated to be involved in the replication process of other types of RNA viruses. Interestingly, by performing immunofluorescence studies, we found that in IBDV-infected cells the mainly nuclear NF45 accumulated at the sites of viral replication in the cytoplasm. NF45 was shown to specifically colocalize with the viral RNA-dependent RNA polymerase VP1, the capsid protein VP2, and the ribonucleoprotein VP3. Immunoprecipitation experiments indicated protein-protein associations between NF45 and VP1, VP2, and VP3. Expression of the individual VP3 or the combination of expression of VP1 and VP3 did not result in a cytoplasmic accumulation of NF45, which, among other data, showed that recruitment of the cellular protein in infected cells functionally correlates with the viral replication process. Since small interfering RNA(siRNA)-mediated downregulation of NF45 resulted in an approximately 5-fold increase of virus yield, our study suggests that NF45, by association with viral proteins, is part of a yet-uncharacterized cellular defense mechanism against IBDV infections.
Stricker
Ruth L O
RL
Poultry Diagnostic and Research Center, University of Georgia, 953 College Station Road, Athens, GA 30602, USA.
Behrens
Sven-Erik
SE
Mundt
Egbert
E
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D007243:Infectious bursal disease virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D028884:Karyopherins / Q000378:metabolism; D051903:Nuclear Factor 45 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology; D000097606:Exportin 1 Protein
D000914:Antibodies, Viral; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017931:DNA Primers; D028884:Karyopherins; D051903:Nuclear Factor 45 Protein; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D014764:Viral Proteins; D000097606:Exportin 1 Protein