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Journal of Virology, April 2007, p. 3264-3271, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02590-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Importance of the Anti-Interferon Capacity of Sendai Virus C Protein for Pathogenicity in Mice

Department of Virology 3, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011,¹ Department of Virology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551,² Center of Research Network for Infectious Diseases, RIKEN, Tokyo 100-0006, Japan³

Received 22 November 2006/ Accepted 2 January 2007

The Sendai virus (SeV) C protein blocks signal transduction of interferon (IFN), thereby counteracting the antiviral actions of IFN. Using HeLa cell lines expressing truncated or mutated SeV C proteins, we found that the C-terminal half has anti-IFN capacity, and that K¹⁵¹A, E¹⁵³A, and R¹⁵⁴A substitutions in the C protein eliminated this capacity. Here, we further created the mutant virus SeV Cm*, in which K¹⁵¹A, E¹⁵³K, and R¹⁵⁷L substitutions in the C protein were introduced without changing the amino acid sequence of overlapped P, V, and W proteins. SeV Cm* was found to lack anti-IFN capacity, as expected. While the growth rate and final yield of SeV Cm* were inferior to those of the wild-type SeV in IFN-responsive, STAT1-positive 2fTGH cells, SeV Cm* grew equivalently to the wild-type SeV in IFN-nonresponsive, STAT1-deficient U3A cells. SeV Cm* was thus shown to maintain multiplication capacity, except that it lacked anti-IFN capacity. Intranasally inoculated SeV Cm* could propagate in the lungs of STAT1^–/– mice but was cleared from those of STAT1^+/+ mice without propagation. It was found that the anti-IFN capacity of the SeV C protein was indispensable for pathogenicity in mice. Conversely, the results show that the innate immunity contributed to elimination of SeV in early stages of infection in the absence of anti-IFN capacity.

Published ahead of print on 10 January 2007.

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