Leader-Containing Uncapped Viral Transcript Activates RIG-I in Antiviral Stress Granules

• Published in: PLoS pathogens Vol. 12; no. 2; p. e1005444
• Main Authors: Oh, Seong-Wook, Onomoto, Koji, Wakimoto, Mai, Onoguchi, Kazuhide, Ishidate, Fumiyoshi, Fujiwara, Takahiro, Yoneyama, Mitsutoshi, Kato, Hiroki, Fujita, Takashi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.02.2016; Public Library of Science (PLoS)
• Subjects: Animals; Biology and life sciences; Care and treatment; DEAD Box Protein 58; DEAD-box RNA Helicases - metabolism; Development and progression; Genetic aspects; Health aspects; Host-virus relationships; Humans; Influenza A virus - genetics; Interferon Regulatory Factor-3 - metabolism; Interferon Type I - metabolism; Interferon-beta - drug effects; Interferon-beta - genetics; Mice; Newcastle disease; Newcastle disease virus - genetics; Receptors, Immunologic; Research and analysis methods; RNA, Viral - drug effects; Signal Transduction - drug effects; Stress, Physiological; Transcription factors; Virulence (Microbiology)
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005444

RIG-I triggers antiviral responses by recognizing viral RNA (vRNA) in the cytoplasm. However, the spatio-temporal dynamics of vRNA sensing and signal transduction remain elusive. We investigated the time course of events in cells infected with Newcastle disease virus (NDV), a non-segmented negative-strand RNA virus. RIG-I was recruited to viral replication complexes (vRC) and triggered minimal primary type I interferon (IFN) production. RIG-I subsequently localized to antiviral stress granules (avSG) induced after vRC formation. The inhibition of avSG attenuated secondary IFN production, suggesting avSG as a platform for efficient vRNA detection. avSG selectively captured positive-strand vRNA, and poly(A)+ RNA induced IFN production. Further investigations suggested that uncapped vRNA derived from read-through transcription was sensed by RIG-I in avSG. These results highlight how viral infections stimulate host stress responses, thereby selectively recruiting uncapped vRNA to avSG, in which RIG-I and other components cooperate in an efficient antiviral program.