Faculty Opinions recommendation of RNA viruses can hijack vertebrate microRNAs to suppress innate immunity.

ABSTRACTHepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV can be sensed by host innate immunity to induce expression of interferons (IFNs) and a number of antiviral effectors. In this study, we found HCV infection induced the expression of neuralized E3 ubiquitin protein ligase 3 (NEURL3), a putative E3 ligase, in a manner that requires the involvement of innate immune sensing but is independent of the IFN action. Furthermore, we showed that NEURL3 inhibited HCV infection while it had little effect on other RNA viruses, including Zika virus (ZIKV), dengue virus (DENV), and vesicular stomatitis virus (VSV). Mechanistic studies demonstrated that NEURL3 inhibited HCV assembly by directly binding HCV envelope glycoprotein E1 to interfere with the E1/E2 heterodimerization, an important prerequisite for virion morphogenesis. Finally, we showed that knockout of NEURL3 significantly enhanced HCV infection. In summary, we identified NEURL3 as a novel inducible antiviral host factor that suppresses HCV assembly. Our results not only shed new insight into how host innate immunity acts against HCV but also revealed a new important biological function for NEURL3.IMPORTANCEThe exact biological function of NEURL3, a putative E3 ligase, remains largely unknown. In this study, we found that NEURL3 could be upregulated upon HCV infection in a manner dependent on pattern recognition receptor-mediated innate immune response. NEURL3 inhibits HCV assembly by directly binding viral E1 envelope glycoprotein to disrupt its interaction with E2, an action that requires its Neuralized homology repeat (NHR) domain but not the RING domain. Furthermore, we found that NEURL3 has a pangenotypic anti-HCV activity and interacts with E1 of genotypes 2a, 1b, 3a, and 6a but does not inhibit other closely related RNA viruses, such as ZIKV, DENV, and VSV. To our knowledge, our study is the first report to demonstrate that NEURL3 functions as an antiviral host factor. Our results not only shed new insight into how host innate immunity acts against HCV, but also revealed a new important biological function for NEURL3.

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Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses

PLoS Pathogens ◽

10.1371/journal.ppat.1009901 ◽

2021 ◽

Vol 17 (9) ◽

pp. e1009901

Author(s):

Min Zhao ◽

Yaolin Zhang ◽

Xiqin Yang ◽

Jiayang Jin ◽

Zhuo Shen ◽

...

Keyword(s):

Innate Immunity ◽

Virus Infection ◽

Nuclear Translocation ◽

Rna Viruses ◽

Rna Virus ◽

Innate Immune ◽

Type I ◽

Gene Promoters ◽

Post Translational Modification

Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.

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Faculty Opinions recommendation of Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1098442.554517 ◽

2007 ◽

Author(s):

Grant McFadden

Keyword(s):

Innate Immunity ◽

Rna Viruses

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Innate Immunity against RNA viruses☆

Reference Module in Biomedical Sciences ◽

10.1016/b978-0-12-801238-3.02607-6 ◽

2015 ◽

Author(s):

L. Martínez-Sobrido ◽

J. Carlos de la Torre

Keyword(s):

Innate Immunity ◽

Rna Viruses

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Chicken DNA Sensing cGAS-STING Signal Pathway Mediates Broad Spectrum Antiviral Functions

Vaccines ◽

10.3390/vaccines8030369 ◽

2020 ◽

Vol 8 (3) ◽

pp. 369

Author(s):

Shuangjie Li ◽

Jie Yang ◽

Yuanyuan Zhu ◽

Xingyu Ji ◽

Kun Wang ◽

...

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Viral Infections ◽

Rna Viruses ◽

Signal Pathway ◽

Synergistic Activity ◽

Dna Sensors ◽

Dna Sensing ◽

Dna Viruses ◽

Antiviral Effects

The innate DNA sensing receptors are one family of pattern recognition receptors and play important roles in antiviral infections, especially DNA viral infections. Among the multiple DNA sensors, cGAS has been studied intensively and is most defined in mammals. However, DNA sensors in chickens have not been much studied, and the chicken cGAS is still not fully understood. In this study, we investigated the chicken cGAS-STING signal axis, revealed its synergistic activity, species-specificity, and the signal essential sites in cGAS. Importantly, both cGAS and STING exhibited antiviral effects against DNA viruses, retroviruses, and RNA viruses, suggesting the broad range antiviral functions and the critical roles in chicken innate immunity.

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