Ubiquitination in the antiviral immune response

Davis, Meredith E.; Gack, Michaela U.

doi:10.1016/j.virol.2015.02.033

Cited by 145 publications

(141 citation statements)

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“…Among the regulators of the IFN pathway, factors involved in protein ubiquitination seem to have special relevance (reviewed in Davis and Gack, 2015). Ubiquitin is a polypeptide that can be covalently bound to a protein substrate (reviewed in Clague et al, 2015).…”

Section: Protein-modulated Control Of the Antiviral Responsementioning

confidence: 99%

“…RIG-I can be ubiquitinated and degraded by RNF125 (Ring Finger Protein 125) and deubiquitinated and stabilized by USP4 (Wang et al, 2013; Luo et al, 2013). Further, RIG-I can be ubiquitinated and activated by TRIM25, which, in turn, can be ubiquitinated and degraded by LUBAC (linear ubiquitin chain assembly complex) and deubiquitinated and stabilized by USP15 (Davis and Gack, 2015) (Fig. 1).…”

Section: Protein-modulated Control Of the Antiviral Responsementioning

confidence: 99%

See 1 more Smart Citation

Long noncoding RNAs in viral infections

Fortes

Morris

2016

Virus Research

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Viral infections induce strong modifications in the cell transcriptome. Among the RNAs whose expression is altered by infection are long noncoding RNAs (lncRNAs). LncRNAs are transcripts with potential to function as RNA molecules. Infected cells may express viral lncRNAs, cellular lncRNAs and chimeric lncRNAs formed by viral and cellular sequences. Some viruses express viral lncRNAs whose function is essential for viral viability. They are transcribed by polymerase II or III and some of them can be processed by unique maturation steps performed by host cell machineries. Some viral lncRNAs control transcription, stability or translation of cellular and viral genes. Surprisingly, similar functions can be exerted by cellular lncRNAs induced by infection. Expression of cellular lncRNAs may be altered in response to viral replication or viral protein expression. However, many cellular lncRNAs respond to the antiviral pathways induced by infection. In fact, many lncRNAs function as positive or negative regulators of the innate antiviral response. Our current knowledge about the identity and function of lncRNAs in infected cells is very limited. However, research into this field has already helped in the identification of novel cellular pathways and may help in the development of therapeutic tools for the treatment of viral infections, autoimmune diseases, neurological disorders and cancer.

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Section: Protein-modulated Control Of the Antiviral Responsementioning

confidence: 99%

Section: Protein-modulated Control Of the Antiviral Responsementioning

confidence: 99%

Long noncoding RNAs in viral infections

Fortes

Morris

2016

Virus Research

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“…Proteins can be polyubiquitinated since ubiquitin itself can serve as a substrate; polyubiquitination is frequently recognized as a signal for protein degradation mediated by the proteasome complex. 374 As ubiquitination has been broadly implicated in multiple cellular processes, including regulation of innate immunity, 375 it is not surprising that viruses have evolved mechanisms to interface with the ubiquitin system.…”

Section: Pro-viral Host Factorsmentioning

confidence: 99%

Biochemistry and Molecular Biology of Flaviviruses

et al. 2018

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Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

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“…Ubiquitin is a small protein of 76 amino acids that is usually attached to lysine residues of proteins by a cascade of enzymes. Ubiquitin molecules are first activated by E1 enzymes, then conjugated by E2 enzymes, and are finally ligated to the substrate by E3 ligases (6). Ubiquitination may result in monoubiquitinated or polyubiquitinated proteins.…”

mentioning

confidence: 99%

“…K48-linked polyubiquitin chains are well known to be recognized by the proteasome, triggering the degradation of the modified substrate. In contrast, K63-linked ubiquitin chains-both the covalently attached and unanchored forms-are generally believed to not trigger the proteasomal degradation of the substrate protein, but rather have important roles in activating signal transduction pathways (6). Mechanistically, K63-linked polyubiquitin can activate signaling pathways by either stabilizing the substrate protein or inducing its multimeric active form, or by facilitating the recruitment of other signaling proteins.…”

mentioning

confidence: 99%