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Signal Transduct Target Ther ; 5(1): 221, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1387195
Viruses ; 13(2)2021 Jan 20.
Article in English | MEDLINE | ID: covidwho-1298428


The nuclear factor κB (NF-κB) family are the master transcription factors that control cell proliferation, apoptosis, the expression of interferons and proinflammatory factors, and viral infection. During viral infection, host innate immune system senses viral products, such as viral nucleic acids, to activate innate defense pathways, including the NF-κB signaling axis, thereby inhibiting viral infection. In these NF-κB signaling pathways, diverse types of ubiquitination have been shown to participate in different steps of the signal cascades. Recent advances find that viruses also modulate the ubiquitination in NF-κB signaling pathways to activate viral gene expression or inhibit host NF-κB activation and inflammation, thereby facilitating viral infection. Understanding the role of ubiquitination in NF-κB signaling during viral infection will advance our knowledge of regulatory mechanisms of NF-κB signaling and pave the avenue for potential antiviral therapeutics. Thus, here we systematically review the ubiquitination in NF-κB signaling, delineate how viruses modulate the NF-κB signaling via ubiquitination and discuss the potential future directions.

Interferons/immunology , NF-kappa B/metabolism , Ubiquitination , Ubiquitins/immunology , Virus Diseases/immunology , Animals , Humans , Protein Binding , Signal Transduction/immunology , Structure-Activity Relationship , Transcriptional Activation/immunology , Virus Diseases/virology
Viruses ; 13(6)2021 06 09.
Article in English | MEDLINE | ID: covidwho-1282639


Mammalian cells have developed an elaborate network of immunoproteins that serve to identify and combat viral pathogens. Interferon-stimulated gene 15 (ISG15) is a 15.2 kDa tandem ubiquitin-like protein (UBL) that is used by specific E1-E2-E3 ubiquitin cascade enzymes to interfere with the activity of viral proteins. Recent biochemical studies have demonstrated how the E3 ligase HECT and RCC1-containing protein 5 (HERC5) regulates ISG15 signaling in response to hepatitis C (HCV), influenza-A (IAV), human immunodeficiency virus (HIV), SARS-CoV-2 and other viral infections. Taken together, the potent antiviral activity displayed by HERC5 and ISG15 make them promising drug targets for the development of novel antiviral therapeutics that can augment the host antiviral response. In this review, we examine the emerging role of ISG15 in antiviral immunity with a particular focus on how HERC5 orchestrates the specific and timely ISGylation of viral proteins in response to infection.

Cytokines/genetics , Interferons/immunology , Intracellular Signaling Peptides and Proteins/genetics , Ubiquitins/genetics , Virus Diseases/immunology , Animals , COVID-19/immunology , Cytokines/immunology , HeLa Cells , Humans , Intracellular Signaling Peptides and Proteins/immunology , Mice , SARS-CoV-2/immunology , Ubiquitins/immunology , Viral Proteins/genetics , Viral Proteins/metabolism