The recognition of RNA virus by the host and the subsequent antiviral responses has been studied for many years. Initial recognition of viral components such as double-stranded RNA (dsRNA) led to the rapid induction of type I interferons and proinflammatory cytokines.

“Recently, Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I) have been implicated in the detection of viral double-stranded RNA and induction of type I interferons.”

Recently, toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I) have been implicated in the detection of viral dsRNA and the induction of type I interferons. However, it was not clear how these viral detectors contributed in vivo in host defense against viruses.

This paper describes how RIG-I is essential for the initial recognition of various RNA viruses in many cell-types except that of plasmacytoid dendritic cells (pDCs). On the other hand, we found that pDCs, which are known to produce high amounts of interferon-α upon viral infection, utilize the TLR system, but not RIG-I. This is the first paper showing the function of RIG-I in vivo, in comparison with that of the TLR system.

This paper describes mice deficient in RIG-I and showed that RIG-I is critical for the induction of type I interferons and interferon-inducible genes in response to several RNA viruses, in most cell types except pDCs. The mice will be a valuable tool for studying the mechanisms of anti-viral host defense in vivo.

Production of type I interferons is vital for the initial host defense against viral infection. Mechanisms for the recognition of viruses have been investigated by various researchers. This paper shows that RIG-I and the TLR system play a critical role in different cell types in the recognition of RNA viruses in vivo.

Modulation of machineries for interferon production will possibly lead to the development of efficient vaccines and the prevention of viral infection. In this aspect, an understanding of the precise mechanism for viral recognition is critical in designing appropriate strategies for clinical applications.

We have been interested in how the innate immune system recognizes pathogen-specific components, and we have been involved in the research of Toll-like receptors. We previously reported that TLR7 and TLR9 are the ligands for viral single-stranded RNA and DNA, respectively.

TLR3 has also been shown to recognize viral dsRNA. Nevertheless, we found that the TLR system is not necessarily essential to antiviral responses in vivo as shown in this paper. Therefore, we further explored novel machineries for the detection of viruses and the production of type I interferons.