Regulation Of The Replication Of Classical Swine Fever Virus By Mitogen-activated Protein Kinase Kinase 2

Classical swine fever (CSF) is a highly contagious and often fatal disease that affects domestic pigs and wild boars, characterized by fever, widespread hemorrhage and immunosuppression. Outbreaks of CSF can cause huge economic losses to the pig industry. As it leads to serious consequence, CSF is an OIE-listed animal disease and must be reported to the World Organization for Animal Health (OIE). CSFV, the pathogen of CSF, is a single-stranded, positive-sense RNA virus, and the diameter of this lipid-enveloped RNA virus is approximately 40-60 nm. The genome consists of a non-capped 5’-UTR (containing the internal ribosome entry site), an open reading frame (ORF), and a 3’-UTR lacking a polyA region. The ORF encodes a 3,898 amino acid polyprotein that undergoes transcriptional and post-transcriptional modifications by a signal peptidase from the host cells and by Npro, NS2, and NS3 proteinase from CSFV. Two precursor proteins and 12 mature proteins are produced from the polyprotein:four structural proteins (C, Ems, E1, and E2), eight non-structural proteins (NPro, P7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B).Mitogen-activated protein kinase kinase/extracellular regulated kinase 2 (MEK2) is an extracellular signaling-regulation kinase (ERK) that plays an important role in activating ERK pathway. It has been reported that MEK2 participates in the replication of many viruses and had an interaction with CSFV. CSFV infection induced activation of ERK pathway and increased the expression of MEK2. The specific inhibitor for ERK pathway can restrain the replication of CSFV.In order to study the effects of the MEK2 expression on the CSFV growth, the lentivirus packing system was used to construct a stable PK-15 cell line overexpressing MEK2 (PK-EGFP-MEK2) and a stable PK-15 cell line with downregulated expression of MEK2 (PK-shMEK2), then the cells were infected with the CSFV Shimen strain. The results showed that overexpression of MEK2 promotes CSFV genomic RNA copy numbers and virus titers, whereas downregulation of MEK2 inhibits viral RNA copy numbers and virus titers.In summary, this present work demonstrated that the host protein MEK2 plays a positive role in the replication of CSFV.