MERTK is a host factor that promotes classical swine fever virus entry and antagonizes innate immune response in PK-15 cells

Autor: Guanglai Zheng, Lian-Feng Li, Yuexiu Zhang, Liang Qu, Wenjing Wang, Miao Li, Shaoxiong Yu, Mo Zhou, Yuzi Luo, Yuan Sun, Muhammad Munir, Su Li, Hua-Ji Qiu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 9, Iss 1, Pp 571-581 (2020)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2020.1738278
Popis: ABSTRACTClassical swine fever virus (CSFV) is a member of the genus Pestivirus in the Flaviviridae family. To date, the host factors required for CSFV entry remain poorly characterized. To identify the functional membrane protein(s) involved in CSFV infection, we analyzed the transcriptomic data from previous studies describing gene expression profiles for CSFV, and found twelve novel candidate proteins. One of these proteins, MERTK, significantly reduced CSFV protein expression by RNA interference screening using a recombinant CSFV that contains a luciferase reporter to measure CSFV protein expression. Furthermore, our results demonstrated that either anti-MERTK antibodies or soluble MERTK ectodomain could reduce CSFV infection in PK-15 cells in a dose-dependent manner. Mechanistically, MERTK interacted with the E2 protein of CSFV and facilitated virus entry. After virus entry, MERTK downregulates of mRNA expression of IFN-β and promotes CSFV infection. Interestingly, the soluble MERTK ectodomain could also reduce the infection of bovine viral diarrhea virus (BVDV), another pestivirus. Taken together, our results suggested that MERTK is a CSFV entry factor that synergistically dampens innate immune responses in PK-15 cells and is also involved in BVDV infection.
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