A single amino acid substitution within the paramyxovirus Sendai virus nucleoprotein is a critical determinant for production of interferon-beta-inducing copyback-type defective interfering genomes

Asuka Yoshida, Ryoko Kawabata, Tomoyuki Honda, Kouji Sakai, Yasushi Ami, Takemasa Sakaguchi, Takashi Irie

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

One of the first defenses against infecting pathogens is the innate immune system activated by cellular recognition of pathogen-associated molecular patterns (PAMPs). Although virus-derived RNA species, especially copyback (cb)-type defective interfering (DI) genomes, have been shown to serve as real PAMPs, which strongly induce interferon-beta (IFN-β) during mononegavirus infection, the mechanisms underlying DI generation remain unclear. Here, for the first time, we identified a single amino acid substitution causing production of cbDI genomes by successful isolation of two distinct types of viral clones with cbDI-producing and cbDI-nonproducing phenotypes from the stock Sendai virus (SeV) strain Cantell, which has been widely used in a number of studies on antiviral innate immunity as a representative IFN-β-inducing virus. IFN-β induction was totally dependent on the presence of a significant amount of cbDI genomecontaining viral particles (DI particles) in the viral stock, but not on deficiency of the IFNantagonistic viral accessory proteins C and V. Comparison of the isolates indicated that a single amino acid substitution found within the N protein of the cbDI-producing clone was enough to cause the emergence of DI genomes. The mutated N protein of the cbDI-producing clone resulted in a lower density of nucleocapsids than that of the DInonproducing clone, probably causing both production of the DI genomes and their formation of a stem-loop structure, which serves as an ideal ligand for RIG-I. These results suggested that the integrity of mononegaviral nucleocapsids might be a critical factor in avoiding the undesirable recognition of infection by host cells.

Original languageEnglish
Article numbere02094-17
JournalJournal of Virology
Volume92
Issue number5
DOIs
Publication statusPublished - Mar 1 2018
Externally publishedYes

Keywords

  • Defective interfering genome
  • Innate immunity
  • Interferons
  • Nucleocapsid
  • Paramyxovirus
  • Sendai virus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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