TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons
Author:
Zhang Boyue1ORCID, Cai Ting1, He Hongling1, Huang Xuezhe1, Luo Yongwen1, Huang Shile23ORCID, Luo Jun1ORCID, Guo Xiaofeng1ORCID
Affiliation:
1. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510651, China 2. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA 3. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA
Abstract
Rabies remains a great threat to public health worldwide. So far, the mechanism of rabies virus (RABV) infection is not fully understood, and there is no effective treatment for rabies. Identifying more host restriction factors of RABV will spur the development of novel therapeutic interventions against rabies. Accumulating studies suggest that tripartite motif-containing (TRIM) proteins have great effects on virus replication. TRIMs control the antiviral responses through either direct interaction with viral proteins or indirect regulation of innate immune signaling molecules in the host. The role of TRIM25 in rabies virus (RABV) infection is poorly understood. Using next-generation sequencing, we found that TRIM25 is upregulated during HEP-Flury infection. Knockdown of TRIM25 enhances HEP-Flury production, while overexpression of TRIM25 suppresses HEP-Flury replication. Knockdown of interferon α and interferon β weakens the anti-RABV response induced by TRIM25 overexpression, and potentiates RABV production. Furthermore, we found that TRIM25 regulates type-I interferon response by targeting retinoic acid-inducible gene I (RIG-I) during HEP-Flury infection. Knockdown of RIG-I weakens the anti-HEP-Flury response induced by TRIM25 overexpression, indicating that TRIM25 regulates RABV production via the RIG-I-IFN axis. In addition, we observed that TRIM25 does not directly interact with HEP-Flury structural proteins, suggesting that TRIM25 regulates HEP-Flury production indirectly. Taken together, our work identifies TRIM25 as a new host factor involved in HEP-Flury infection, which may be a potential target for the development of antiviral drugs against RABV.
Funder
National Key Research and Development Program Basic and Applied Basic Research Project of Guangzhou Basic Research Program National Natural Science Foundation of China Guangdong Provincial Natural Science Foundation of China
Subject
Genetics (clinical),Genetics
Reference64 articles.
1. Hampson, K., Coudeville, L., Lembo, T., Sambo, M., Kieffer, A., Attlan, M., Barrat, J., Blanton, J.D., Briggs, D.J., and Cleaveland, S. (2015). Estimating the global burden of endemic canine rabies. PLoS Negl. Trop. Dis., 9. 2. Replication strategies of rabies virus;Finke;Virus Res.,2005 3. Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus;Leroy;Neurobiol. Dis.,2006 4. Yang, X., Wan, M., Cai, L., Hou, A., Sun, B., Zhou, Y., Gao, F., Su, W., and Jiang, C. (2021). Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells. Viruses, 14. 5. Relationship of interferon synthesis and the resistance of mice infected with street rabies virus;Mendonca;Braz. J. Med. Biol. Res.,1994
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