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

Zheng, G. and Li, L.-F. and Zhang, Y. and Qu, L. and Wang, W. and Li, M. and Yu, S. and Zhou, M. and Luo, Y. and Sun, Y. and Munir, M. and Li, S. and Qiu, H.-J. (2020) MERTK is a host factor that promotes classical swine fever virus entry and antagonizes innate immune response in PK-15 cells. Emerging Microbes and Infections, 9 (1). pp. 571-581.

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Abstract

Classical 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.

Item Type:
Journal Article
Journal or Publication Title:
Emerging Microbes and Infections
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2400/2405
Subjects:
ID Code:
142737
Deposited By:
Deposited On:
22 Apr 2020 12:35
Refereed?:
Yes
Published?:
Published
Last Modified:
30 Sep 2020 09:44