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Journal of Virology, September 2000, p. 7834-7841, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Involvement of the Zinc-Binding Capacity of Sendai Virus V Protein in Viral Pathogenesis

Cheng Huang,1 Katsuhiro Kiyotani,1 Yutaka Fujii,1 Noriko Fukuhara,1 Atsushi Kato,2,dagger Yoshiyuki Nagai,2,Dagger Tetsuya Yoshida,1 and Takemasa Sakaguchi1,*

Department of Bacteriology, Hiroshima University School of Medicine, Hiroshima 734-8551,1 and Department of Viral Infection, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,2 Japan

Received 1 March 2000/Accepted 30 May 2000

The V protein of Sendai virus (SeV) is nonessential to virus replication in cell culture but indispensable to viral pathogenicity in mice. The highly conserved cysteine-rich zinc finger-like domain in its carboxyl terminus is believed to be responsible for this viral pathogenicity. In the present study, we showed that the cysteine-rich domain of the SeV V protein could actually bind zinc by using glutathione-S-transferase fusion proteins. When the seven conserved cysteine residues at positions 337, 341, 353, 355, 358, 362, and 365 were replaced individually, the zinc-binding capacities of the mutant proteins were greatly impaired, ranging from 22 to 68% of that of the wild type. We then recovered two mutant SeVs from cDNA, which have V-C341S and V-C365R mutations and represent maximal and minimal zinc-binding capacities among the corresponding mutant fusion proteins, respectively. The mutant viruses showed viral protein synthesis and growth patterns similar to those of wild-type SeV in cultured cells. However, the mutant viruses were strongly attenuated in mice in a way similar to that of SeV VDelta C, which has a truncated V protein lacking the cysteine-rich domain, by exhibiting earlier viral clearance from the mouse lung and less virulence to mice. We therefore conclude that the zinc-binding capacity of the V protein is involved in viral pathogenesis.

* Corresponding author. Mailing address: Department of Bacteriology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Phone: 81-82-257-5157. Fax: 81-82-257-5159. E-mail: takemasa{at}mcai.med.hiroshima-u.ac.jp.

dagger Present address: Department of Viral Diseases and Vaccine Control, National Institute of Infectious Diseases, Musashi-Murayama 208-0011, Japan.

Dagger Present address: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.

Journal of Virology, September 2000, p. 7834-7841, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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