Hitting the right button: MAVS-mediated defense against HAV infection

Knolle, Percy A.

doi:10.1038/cr.2016.139

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Previous studies have reported that picornaviruses exert various strategies to evade host innate immune responses through certain viral proteins, such as L pro , VP2, VP3, 2A pro , 2C pro , 3A pro , and 3C pro (17,18,(25)(26)(27)(28)(29)(30)(31). In this study, we found that the overexpression of SVV proteins VP2, 3C pro , and 3D reduced Sev-induced IFN-␤ production (Fig.…”

Section: Resultssupporting

confidence: 59%

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

Qian

Fan

Liu

et al. 2017

J Virol

107

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Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-␤ (TRIF), and TRAF family member-associated NF-B activator (TANK), via viral 3C protease (3C pro ). SVV 3C pro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-B activation. SVV was also found to be sensitive to IFN-␤. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C pro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for the Toll-like receptor 3 (TLR3)-mediated and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated signaling pathway. We also found that SVV is sensitive to IFN-␤. These findings increase our understanding of the interaction between SVV and host innate immunity.

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Section: Resultssupporting

confidence: 59%

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

Qian

Fan

Liu

et al. 2017

J Virol

107

View full text Add to dashboard Cite

show abstract

“…As for the RIG-I pathway, RIG-I first recognizes exogenous RNA, then the adaptor MAVS forms prion-like aggregates on the mitochondria to recruit downstream kinases and thereby phosphorylates IRF7 to regulate IFNs and ISGs expression. 35 , 48 In HBV-infected hepatocytes, RIG-I recognizes HBV pgRNA and induces IFN-λ expression. 33 In this study, we found that NFATc3 participated in the RIG-I pathway to enhance type I and type III IFN responses in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%