Involvement of the zinc-binding capacity of Sendai virus V protein in viral pathogenesis

Cheng Huang, K. Kiyotani, Y. Fujii, N. Fukuhara, A. Kato, Y. Nagai, T. Yoshida, T. Sakaguchi

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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 V(ΔC), 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.

Original languageEnglish (US)
Pages (from-to)7834-7841
Number of pages8
JournalJournal of Virology
Volume74
Issue number17
DOIs
StatePublished - Sep 4 2000
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Huang, C., Kiyotani, K., Fujii, Y., Fukuhara, N., Kato, A., Nagai, Y., Yoshida, T., & Sakaguchi, T. (2000). Involvement of the zinc-binding capacity of Sendai virus V protein in viral pathogenesis. Journal of Virology, 74(17), 7834-7841. https://doi.org/10.1128/JVI.74.17.7834-7841.2000