The influenza B virus nonstructural NS1 protein is essential for efficient viral growth and antagonizes beta interferon induction.
We analyzed the functions of the influenza B virus nonstructural NS1-B protein, both by utilizing a constructed mutant virus (Delta NS1-B) lacking the NS1 gene and by testing the activities of the protein when expressed in cells. The mutant virus replicated to intermediate levels in 6-day-old embryonated chicken eggs that contain an immature interferon (IFN) system, whereas older eggs did not support viral propagation to a significant extent. The Delta NS1-B virus was a substantially stronger inducer of beta IFN (IFN-beta) transcripts in human lung epithelial cells than the wild type, and furthermore, transiently expressed NS1-B protein efficiently inhibited virus-dependent activation of the IFN-beta promoter. Interestingly, replication of the Delta NS1-B knockout virus was attenuated by more than 4 orders of magnitude in tissue culture cells containing or lacking functional IFN-alpha/beta genes. These findings show that the NS1-B protein functions as a viral IFN antagonist and indicate a further requirement of this protein for efficient viral replication that is unrelated to blocking IFN effects.
Dauber
Bianca
B
Robert Koch-Institut, 13353 Berlin, Germany.
Heins
Gudrun
G
Wolff
Thorsten
T
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004285:Dogs; D006801:Humans; D009981:Influenza B virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009154:Mutation; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta