Ubiquitin in the activation and attenuation of innate antiviral immunity
نویسندگان
چکیده
Viral infection activates danger signals that are transmitted via the retinoic acid-inducible gene 1-like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. This places host cells in an antiviral posture by up-regulating antiviral cytokines including type-I interferon (IFN-I). Ubiquitin modifications and cross-talk between proteins within these signaling cascades potentiate IFN-I expression, and inversely, a growing number of viruses are found to weaponize the ubiquitin modification system to suppress IFN-I. Here we review how host- and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression.
منابع مشابه
Hepatitis B Virus-Induced Parkin-Dependent Recruitment of Linear Ubiquitin Assembly Complex (LUBAC) to Mitochondria and Attenuation of Innate Immunity
Hepatitis B virus (HBV) suppresses innate immune signaling to establish persistent infection. Although HBV is a DNA virus, its pre-genomic RNA (pgRNA) can be sensed by RIG-I and activates MAVS to mediate interferon (IFN) λ synthesis. Despite of the activation of RIG-I-MAVS axis by pgRNA, the underlying mechanism explaining how HBV infection fails to induce interferon-αβ (IFN) synthesis remained...
متن کاملGenome-wide computational prediction of miRNAs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed target genes involved in pulmonary vasculature and antiviral innate immunity
The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)in China threatened humankind worldwide. The coronaviruses contains the largest RNA genome among all other known RNA viruses, therefore the disease etiology can be understood by analyzing the genome sequence of SARS-CoV-2. In this study, we used an ab-intio based computational tool VMir to scan the complete geno...
متن کاملLys29-linkage of ASK1 by Skp1−Cullin 1−Fbxo21 ubiquitin ligase complex is required for antiviral innate response
Protein ubiquitination regulated by ubiquitin ligases plays important roles in innate immunity. However, key regulators of ubiquitination during innate response and roles of new types of ubiquitination (apart from Lys48- and Lys63-linkage) in control of innate signaling have not been clearly understood. Here we report that F-box only protein Fbxo21, a functionally unknown component of SCF (Skp1...
متن کاملReconstitution of the RIG-I Pathway Reveals a Signaling Role of Unanchored Polyubiquitin Chains in Innate Immunity
RIG-I detects invading viral RNA and activates the transcription factors NF-kappaB and IRF3 through the mitochondrial protein MAVS. Here we show that RNA bearing 5'-triphosphate strongly activates the RIG-I-IRF3 signaling cascade in a reconstituted system composed of RIG-I, mitochondria, and cytosol. Activation of RIG-I requires not only RNA but also polyubiquitin chains linked through lysine 6...
متن کاملUbe2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in antiviral innate immunity
Innate immunity plays a pivotal role in virus infection. RIG-I senses viral RNA and initiates an effective innate immune response for type I interferon production. To transduce RIG-I-mediated antiviral signalling, a mitochondrial protein MAVS forms prion-like aggregates to activate downstream kinases and transcription factors. However, the activation mechanism of RIG-I is incompletely understoo...
متن کامل