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Journal of Virology, February 2004, p. 1865-1872, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1865-1872.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Influenza B Virus Nonstructural NS1 Protein Is Essential for Efficient Viral Growth and Antagonizes Beta Interferon Induction

Robert Koch-Institut, 13353 Berlin, Germany

Received 14 August 2003/ Accepted 30 October 2003

We analyzed the functions of the influenza B virus nonstructural NS1-B protein, both by utilizing a constructed mutant virus (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 NS1-B virus was a substantially stronger inducer of beta IFN (IFN-ß) 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-ß promoter. Interestingly, replication of the NS1-B knockout virus was attenuated by more than 4 orders of magnitude in tissue culture cells containing or lacking functional IFN-/ß 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.

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