Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation
Viral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escap...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/2/182 |
| _version_ | 1827597792495796224 |
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| author | Cindy Chiang Guanqun Liu Michaela U. Gack |
| author_facet | Cindy Chiang Guanqun Liu Michaela U. Gack |
| author_sort | Cindy Chiang |
| collection | DOAJ |
| description | Viral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escape strategies are viral mechanisms to dysregulate the post-translational modifications (PTMs) that play pivotal roles in RLR regulation. In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. Key viral strategies to evade RLR signaling include direct targeting of ubiquitin E3 ligases, active deubiquitination using viral deubiquitinating enzymes (DUBs), and the upregulation of cellular DUBs that regulate RLR signaling. Additionally, we summarize emerging new evidence that shows that enzymes of certain coronaviruses such as SARS-CoV-2, the causative agent of the current COVID-19 pandemic, actively deISGylate key molecules in the RLR pathway to escape type I interferon (IFN)-mediated antiviral responses. Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines. |
| first_indexed | 2024-03-09T03:39:21Z |
| format | Article |
| id | doaj.art-598a81bdb1fb427880b63fdbaf741991 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:39:21Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-598a81bdb1fb427880b63fdbaf7419912023-12-03T14:43:30ZengMDPI AGViruses1999-49152021-01-0113218210.3390/v13020182Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylationCindy Chiang0Guanqun Liu1Michaela U. Gack2Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USAFlorida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USAFlorida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USAViral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escape strategies are viral mechanisms to dysregulate the post-translational modifications (PTMs) that play pivotal roles in RLR regulation. In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. Key viral strategies to evade RLR signaling include direct targeting of ubiquitin E3 ligases, active deubiquitination using viral deubiquitinating enzymes (DUBs), and the upregulation of cellular DUBs that regulate RLR signaling. Additionally, we summarize emerging new evidence that shows that enzymes of certain coronaviruses such as SARS-CoV-2, the causative agent of the current COVID-19 pandemic, actively deISGylate key molecules in the RLR pathway to escape type I interferon (IFN)-mediated antiviral responses. Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines.https://www.mdpi.com/1999-4915/13/2/182viral evasionubiquitinISG15innate immunityinterferon |
| spellingShingle | Cindy Chiang Guanqun Liu Michaela U. Gack Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation Viruses viral evasion ubiquitin ISG15 innate immunity interferon |
| title | Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation |
| title_full | Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation |
| title_fullStr | Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation |
| title_full_unstemmed | Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation |
| title_short | Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation |
| title_sort | viral evasion of rig i like receptor mediated immunity through dysregulation of ubiquitination and isgylation |
| topic | viral evasion ubiquitin ISG15 innate immunity interferon |
| url | https://www.mdpi.com/1999-4915/13/2/182 |
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