Abstract

The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5′-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures.

Highlights

  • Eukaryotic cells are equipped with various defense mechanisms to detect and respond to viral infections rapidly

  • We found that some types of unusual RNA species that were distinguishable according to specific detectability by the antidsRNA antibody or Fluorescence In Situ Hybridization (FISH) analysis were produced during the viral replication of IFN-inducing Sendai virus (SeV), but not IFN-non-inducing SeV strains, and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner

  • When cells were infected with 4C(-), G3BP1-positive granular structures were observed in almost 90% of SeV antigen-positive cells, and were considered to be stress granules (SGs)-like structures since TIA-1-related protein (TIAR)

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Summary

Introduction

Eukaryotic cells are equipped with various defense mechanisms to detect and respond to viral infections rapidly. The interferon (IFN) system is one of the most important natural defenses of mammalian cells in the early phase of viral infection. Host cells sense the invasion of viruses by recognizing their pathogen-associated molecular patterns (PAMPs), including the structural characteristics of viral RNAs that differentiate them from cellular RNAs (Akira et al, 2006). Selective accumulation of IFN-β-inducing viral RNA and genetics gene 2 (LGP2). This is followed by the subsequent induction of IFN-β (Gitlin et al, 2006; Kaisho and Akira, 2006; Saito et al, 2007). Autocrine or paracrine IFNs bind to IFN receptors on the cell surface, leading to the expression of 100s of IFN-stimulated genes (ISGs) through the Jak/STAT signaling pathway, which exerts various antiviral effects (Akira et al, 2006)

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