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Updated: Dec 26, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
MERTK is a host factor that promotes classical swine fever virus entry and antagonizes innate immune response in
Guanglai Zheng1, Lian-Feng Li1, Yuexiu Zhang1
1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.
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.
Insights
This study identifies MERTK as a crucial host factor for Classical swine fever virus (CSFV) entry and replication. MERTK facilitates CSFV infection by interacting with the virus and suppressing innate immune responses.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Classical swine fever virus (CSFV) poses a significant threat to swine populations globally.
- The host factors governing CSFV entry and replication are not fully understood, hindering effective control strategies.
Purpose of the Study:
- To identify host membrane proteins essential for CSFV infection.
- To elucidate the mechanism by which MERTK influences CSFV pathogenesis.
Main Methods:
- Transcriptomic data analysis to identify candidate host factors.
- RNA interference screening using a CSFV-luciferase reporter system.
- In vitro assays using anti-MERTK antibodies and soluble MERTK ectodomain to assess viral inhibition.
- Co-immunoprecipitation to confirm MERTK-CSFV E2 protein interaction.
- Analysis of Interferon-beta (IFN-β) mRNA expression.
Main Results:
- Twelve novel candidate host proteins were identified, with MERTK showing significant impact on CSFV replication.
- MERTK was confirmed as a CSFV entry factor, interacting with the viral E2 protein.
- Anti-MERTK antibodies and soluble MERTK ectodomain dose-dependently reduced CSFV infection in PK-15 cells.
- MERTK was found to downregulate IFN-β mRNA expression, thereby promoting CSFV infection.
- Soluble MERTK ectodomain also inhibited infection by bovine viral diarrhea virus (BVDV), another pestivirus.
Conclusions:
- MERTK is a critical host factor for CSFV entry and replication.
- MERTK actively dampens innate immune responses, specifically IFN-β production, to facilitate viral infection.
- MERTK represents a potential therapeutic target for CSFV and possibly other pestivirus infections.
