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

41 Citations (Scopus)

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

Fingerprint

Sendai virus
viral proteins
binding capacity
Cysteine
Zinc
pathogenesis
zinc
Virulence
Mutant Proteins
cysteine
mutants
proteins
Viruses
mice
Proteins
Zinc Fingers
Viral Proteins
Virus Replication
Glutathione Transferase
pathogenicity

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Huang, C., Kiyotani, K., Fujii, Y., Fukuhara, N., Kato, A., Nagai, Y., ... 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

Involvement of the zinc-binding capacity of Sendai virus V protein in viral pathogenesis. / Huang, Cheng; Kiyotani, K.; Fujii, Y.; Fukuhara, N.; Kato, A.; Nagai, Y.; Yoshida, T.; Sakaguchi, T.

In: Journal of Virology, Vol. 74, No. 17, 04.09.2000, p. 7834-7841.

Research output: Contribution to journalArticle

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, vol. 74, no. 17, pp. 7834-7841. https://doi.org/10.1128/JVI.74.17.7834-7841.2000
Huang, Cheng ; Kiyotani, K. ; Fujii, Y. ; Fukuhara, N. ; Kato, A. ; Nagai, Y. ; Yoshida, T. ; Sakaguchi, T. / Involvement of the zinc-binding capacity of Sendai virus V protein in viral pathogenesis. In: Journal of Virology. 2000 ; Vol. 74, No. 17. pp. 7834-7841.
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