Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - MERTK is a host factor that promotes classical swine fever virus entry and antagonizes innate immune response in PK-15 cells
AU - Zheng, G.
AU - Li, L.-F.
AU - Zhang, Y.
AU - Qu, L.
AU - Wang, W.
AU - Li, M.
AU - Yu, S.
AU - Zhou, M.
AU - Luo, Y.
AU - Sun, Y.
AU - Munir, M.
AU - Li, S.
AU - Qiu, H.-J.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - classical swine fever virus
KW - entry
KW - innate immune response
KW - MERTK
KW - TAM receptors
U2 - 10.1080/22221751.2020.1738278
DO - 10.1080/22221751.2020.1738278
M3 - Journal article
C2 - 32172658
VL - 9
SP - 571
EP - 581
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
IS - 1
ER -