Rotavirus NSP1 Inhibits Expression of Type I Interferon by Antagonizing the Function of Interferon Regulatory Factors IRF3, IRF5, and IRF7
Mario Barro,John T. Patton +1 more
Reads0
Chats0
TLDR
It is determined that, in comparison to wild-type rotavirus NSP1 grow to lower titers in some cell lines and that this poor growth phenotype is due to their failure to suppress IFN expression, and evidence is provided that rotaviruses encoding wild- type N SP1 subvert IFN signaling by inducing the degradation of not only IRF3, but also IRF7.Abstract:
Secretion of interferon (IFN) by virus-infected cells is essential for activating autocrine and paracrine pathways that promote cellular transition to an antiviral state. In most mammalian cells, IFN production is initiated by the activation of constitutively expressed IFN regulatory factor 3, IRF3, which in turn leads to the induction of IRF7, the “master regulator” of IFN type I synthesis (alpha/beta IFN). Previous studies established that rotavirus NSP1 antagonizes IFN signaling by inducing IRF3 degradation. In the present study, we have determined that, in comparison to wild-type rotaviruses, rotaviruses encoding defective NSP1 grow to lower titers in some cell lines and that this poor growth phenotype is due to their failure to suppress IFN expression. Furthermore, we provide evidence that rotaviruses encoding wild-type NSP1 subvert IFN signaling by inducing the degradation of not only IRF3, but also IRF7, with both events occurring through proteasome-dependent processes that proceed with similar efficiencies. The capacity of NSP1 to induce IRF7 degradation may allow rotavirus to move across the gut barrier by enabling the virus to replicate in specialized trafficking cells (dendritic cells and macrophages) that constitutively express IRF7. Along with IRF3 and IRF7, NSP1 was found to induce the degradation of IRF5, a factor that upregulates IFN expression and that is involved in triggering apoptosis during viral infection. Our analysis suggests that NSP1 mediates the degradation of IRF3, IRF5, and IRF7 by recognizing a common element of IRF proteins, thereby allowing NSP1 to act as a broad-spectrum antagonist of IRF function.read more
Citations
More filters
Journal ArticleDOI
Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.
TL;DR: Applied aspects that arise from an increase in knowledge in this area are described, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.
Journal ArticleDOI
The IRF Family Transcription Factors in Immunity and Oncogenesis
TL;DR: The role of several IRF family members in the regulation of the cell cycle and apoptosis has important implications for understanding susceptibility to and progression of several cancers.
Journal ArticleDOI
Viral evasion and subversion of pattern-recognition receptor signalling
TL;DR: Accumulating evidence on how viral infection and PRR signalling pathways intersect is providing further insights into the function of the pathways involved, their constituent proteins and ways in which they could be manipulated therapeutically.
Journal ArticleDOI
IRF7: activation, regulation, modification and function
TL;DR: Interferon regulatory factor 7 was originally identified in the context of Epstein–Barr virus infection, and has since emerged as the crucial regulator of type I interferons (IFNs) against pathogenic infections, which activate IRF7 by triggering signaling cascades from pathogen recognition receptors (PRRs) that recognize pathogenic nucleic acids.
Journal ArticleDOI
Rotaviruses: From Pathogenesis to Vaccination
Harry B. Greenberg,Mary K. Estes +1 more
TL;DR: Molecular biology studies of rotavirus replication and pathogenesis have identified unique viral targets that might be useful in developing therapies for immunocompromised children with chronic infections.
References
More filters
Journal ArticleDOI
IRF-7 is the master regulator of type-I interferon-dependent immune responses
Kenya Honda,Hideyuki Yanai,Hideo Negishi,Masataka Asagiri,Mitsuharu Sato,Tatsuaki Mizutani,Naoya Shimada,Yusuke Ohba,Yusuke Ohba,Akinori Takaoka,Nobuaki Yoshida,Tadatsugu Taniguchi +11 more
TL;DR: It is shown that mice deficient in the Irf7 gene are more vulnerable than Myd88-/- mice to viral infection, and this correlates with a marked decrease in serum IFN levels, indicating the importance of the IRF-7-dependent induction of systemic IFN responses for innate antiviral immunity.
Journal ArticleDOI
IRF family of transcription factors as regulators of host defense
TL;DR: Their functional roles, through interactions with their own or other members of the family of transcription factors, are becoming clearer in the regulation of host defense, such as innate and adaptive immune responses and oncogenesis.
Journal ArticleDOI
IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.
Kenya Honda,Tadatsugu Taniguchi +1 more
TL;DR: The interferon-regulatory factor family of transcription factors was initially found to be involved in the induction of genes that encode type I interferons but has now been shown to have functionally diverse roles in the regulation of the immune system.
Journal ArticleDOI
Distinct and Essential Roles of Transcription Factors IRF-3 and IRF-7 in Response to Viruses for IFN-α/β Gene Induction
Mitsuharu Sato,Hirofumi Suemori,Naoki Hata,Masataka Asagiri,Kouetsu Ogasawara,Kazuki Nakao,Takeo Nakaya,Motoya Katsuki,Shigeru Noguchi,Nobuyuki Tanaka,Tadatsugu Taniguchi +10 more
TL;DR: The results demonstrate the essential and distinct roles of the two factors, which together ensure the transcriptional efficiency and diversity of IFN-alpha/beta genes for the antiviral response.
Journal ArticleDOI
RING finger proteins: mediators of ubiquitin ligase activity.
TL;DR: The field of intracellular protein degradation now leaves the era where mediators of substrate-specific ubiquitination were scarce and enters a new and exciting phase where databases provide us with a large number of candidate E3s awaiting characterization.
Related Papers (5)
Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3.
Mario Barro,John T. Patton +1 more