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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #382742

Research Project: Intervention Strategies to Control Endemic and New and Emerging Viral Diseases of Swine

Location: Virus and Prion Research

Title: Inhibition of antiviral innate immunity by Foot-and-Mouth Disease Virus Lpro through interaction with N-terminal domain of swine RNase L

Author
item SUI, CHAO - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES
item JIANG, DANDAN - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES
item WU, XIANGJU - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES
item LIU, SIDANG - SHANDONG AGRICULTURAL UNIVERSITY
item LI, FENG - SOUTH DAKOTA STATE UNIVERSITY
item PAN, LI - CHINESE ACADEMY OF AGRICULTURAL SCIENCES
item CONG, XIAOYAN - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES
item LI, JUNTONG - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES
item YOO, DONGWAN - UNIVERSITY OF ILLINOIS
item ROCK, DANIEL - UNIVERSITY OF ILLINOIS
item Miller, Laura
item LEE, CHANGHEE - KYUNGPOOK NATIONAL UNIVERSITY
item DU, YIJUN - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES
item QI, JING - SHANDONG ACADEMY OF AGRICULTURAL SCIENCES

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/28/2021
Publication Date: 7/12/2021
Citation: Sui, C., Jiang, D., Wu, X., Liu, S., Li, F., Pan, L., Cong, X., Li, J., Yoo, D., Rock, D.L., Miller, L.C., Lee, C., Du, Y., Qi, J. 2021. Inhibition of antiviral innate immunity by Foot-and-Mouth Disease Virus Lpro through interaction with N-terminal domain of swine RNase L. Journal of Virology. 95(15). https://doi.org/10.1128/JVI.00361-21.
DOI: https://doi.org/10.1128/JVI.00361-21

Interpretive Summary: Foot-and-mouth diseases virus (FMDV) is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. Here we show that Lpro of FMDV antagonizes the OAS/RNase L pathway, an important interferon effector pathway, by interacting with N-terminal domain of sRNase L. Interestingly, such a virus-host interaction is species-specific because the interaction is detected only in swine cells, not in human, monkey, or canine cells. Furthermore, Lpro relieves the inhibitory effect of sRNase L on production of ISGs and inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.

Technical Abstract: Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (Lpro) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 2’,5’-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of Lpro deletion virus were significantly lower than those of wild type FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that Lpro interfered with OAS/RNase L pathway by interacting with N-terminal domain of swine RNase L (sRNase L). Remarkably, Lpro of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV Lpro relieved the inhibitory effect of sRNase L on production of interferon-stimulated genes (ISGs), in addition to inhibit cellular apoptosis. Taken together, these results demonstrate a novel mechanism that Lpro utilizes to escape the OAS/RNase L-mediated antiviral defense pathway.