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Numerous strategies have been explored to combat rabies; however, their efficacy has always been unsatisfactory. We previously reported a new drug, PGG, which possesses a potent inhibitory activity on RABV replication. Herein, we describe the underlying mechanisms by which PGG exerts its anti-RABV activity. Our results show that RABV induces overactivation of STAT3 in BHK-21 cells, which facilitates viral replication. Importantly, PGG effectively inhibits the activity of STAT3 by disrupting the expression of miR-455-5p and increases the level of SOCS3 by directly targeting the 3\u2032 UTR of SOCS3. Furthermore, the downregulated STAT3 inhibits the production of IL-6, thereby contributing to a reduction in the inflammatory response\n            <jats:italic>in vivo<\/jats:italic>\n            . Our study indicates that PGG effectively inhibits the replication of RABV by the miR-455-5p\/SOCS3\/STAT3\/IL-6-dependent pathway.\n          <\/jats:p>","DOI":"10.1128\/jvi.00539-19","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T11:42:45Z","timestamp":1561635765000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Pentagalloylglucose Inhibits the Replication of Rabies Virus via Mediation of the miR-455\/SOCS3\/STAT3\/IL-6 Pathway"],"prefix":"10.1128","volume":"93","author":[{"given":"Zhongzhong","family":"Tu","sequence":"first","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Jilin, People\u2019s Republic of 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