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Journal of Virology, February 2002, p. 1617-1625, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1617-1625.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

NS1 Protein of Influenza A Virus Down-Regulates Apoptosis

O. P. Zhirnov,1 T. E. Konakova,1 T. Wolff,2 and H.-D. Klenk3*

D. I. Ivanovsky Institute of Virology, Moscow 123098, Russia,1 Robert-Koch-Institut, 13353 Berlin, ,2 Institut für Virologie, Philipps-Universität, 35037 Marburg, Germany3

Received 17 July 2001/ Accepted 6 November 2001

Wild-type (WT) influenza A/PR/8/34 virus and its variant lacking the NS1 gene (delNS1) have been compared for their ability to mediate apoptosis in cultured cells and chicken embryos. Cell morphology, fragmentation of chromatin DNA, and caspase-dependent cleavage of the viral NP protein have been used as markers for apoptosis. Another marker was caspase cleavage of the viral M2 protein, which was also found to occur in an apoptosis-specific manner. In interferon (IFN)-competent host systems, such as MDCK cells, chicken fibroblasts, and 7-day-old chicken embryos, delNS1 virus induced apoptosis more rapidly and more efficiently than WT virus. As a consequence, delNS1 virus was also more lethal for chicken embryos than WT virus. In IFN-deficient Vero cells, however, apoptosis was delayed and developed with similar intensity after infection with both viruses. Taken together, these data indicate that the IFN antagonistic NS1 protein of influenza A viruses has IFN-dependent antiapoptotic potential.

* Corresponding author. Mailing address: Institut für Virologie, Postfach 2360, 35011 Marburg, Germany. Phone: 49 6421/28 66253. Fax: 49 6421/28 68962. E-mail: klenk{at}0040mailer.uni-marburg.de.

Journal of Virology, February 2002, p. 1617-1625, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1617-1625.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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