Abstract
Serine incorporator 5 (SERINC5), a multipass transmembrane protein, protects cells from viral infections. The mechanism by which SERINC5 protects against classical swine fever virus (CSFV) infection is unknown. In this study, overexpression of SERINC5 in PK-15 and 3D4/2 cells significantly inhibited the growth of CSFV, whereas SERINC5 silencing enhanced CSFV growth. Additionally, CSFV infection reduced SERINC5 production in cells and tissues. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify and analyze protein and peptide molecules that potentially interact with SERINC5. A total of 33 cellular protein candidates were identified. Next, SERINC5 was shown to interact with melanoma differentiation-associated protein 5 (MDA5) by yeast two-hybrid, protein co-localization and co-immunoprecipitation assays. Furthermore, SERINC5 enhanced MDA5-mediated type I interferon (IFN) signaling in a dose-dependent manner. Our results suggest that the anti-CSFV effect of SERINC5 is dependent on the activation of the type I IFN, which may function along with MDA5. The inhibitory effect of SERINC5 on CSFV was disappeared when the endogenous expression of MDA5 was silenced using siRNA, suggesting that SERINC5 exerts an anti-CSFV effect in an MDA5-dependent manner. Our study demonstrated a novel link between SERINC5 and MDA5 in the inhibition of CSFV replication via the type I IFN signaling pathway.
Highlights
Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly contagious viral disease of pigs listed by the World Organization for Animal Health (OIE) (Ali et al, 1999; Becher et al, 2003)
These results demonstrate an inhibitory effect of Serine incorporator 5 (SERINC5) on CSFV replication
SERINC5 is a novel host restriction factor that defends against viral infections, including that of murine leukemia virus (MLV), human immune deficiency virus (HIV) and equine infectious anemia virus (EIAV) (Ahi et al, 2016; Chande et al, 2016; Trautz et al, 2016)
Summary
Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly contagious viral disease of pigs listed by the World Organization for Animal Health (OIE) (Ali et al, 1999; Becher et al, 2003). Infected animals generally show different clinical signs, including high fever, respiratory and gastrointestinal signs, hemorrhage, leukopenia, abortions, neurological dysfunction and high mortality, which brings enormous loss to the pig industry worldwide Extensive efforts have been made to control the spread of CSF disease through stamping-out (non-vaccination) and mass vaccination strategies, there are no specific therapeutic drugs currently available. To effectively control CSFV infection through drugs or vaccines, a better understanding of the relationship between CSFV and host is required. The mechanism of CSFV replication has been well characterized, the current understanding of CSFV pathogenesis is still limited
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
