Porcine RACK1 negatively regulates the infection of classical swine fever virus and the NF-κB activation in PK-15 cells.

Classical swine fever (CSF) is one of the main viral diseases of swine worldwide. The causative pathogen is CSF virus (CSFV), a small enveloped RNA virus of the genus Pestivirus. Activation of NF-κB is a hallmark of most viral infections and the viral pathogens frequently kidnap NF-κB pathway for their own advantages, however, it is unclear or even controversial about whether CSFV infection can activate NF-κB signal pathway. RACK1 was shown as an interacting host protein with CSFV NS5A protein, but no studies so far have clearly defined the role of RACK1 during CSFV infection and NF-κB activation. In this study, to properly address these open questions, using RT-qPCR, western blot, indirect fluorescence staining, siRNA knockdown and protein overexpression techniques, we demonstrated that CSFV infection reduced the RACK1 expression at both mRNA and protein levels in PK-15 cells. Downregulation of cellular RACK1 enhanced CSFV infection and subsequent NF-κB activation, while RACK1 overexpression inhibited CSFV infection and the NF-κB activation. In conclusion, RACK1 is a negative cellular regulator for CSFV infection and NF-κB activation in PK-15 cells. Our work addressed a novel aspect concerning the regulation of innate antiviral immune response during CSFV infection. This study may provide some insights into the molecular mechanisms of CSFV infection in swine. However, the elaborate mechanism by which CSFV regulates NF-κB activation and how RACK1 plays its roles in CSFV infection and NF-κB induction require further in-depth studies.

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