Role of double-stranded RNA and N pro of classical swine fever virus in the activation of monocyte-derived dendritic cells

Abstract

Classical swine fever virus (CSFV) is a noncytopathogenic (ncp) positive-sense RNA virus that replicates in myeloid cells including macrophages and dendritic cells (DC). The virus does not induce type I interferon (IFN-α/β), which in macrophages has been related to the presence of the viral N pro gene. In the present work, the role of viral double-stranded (ds)RNA and N pro in the virus–host cell interaction has been analyzed. Higher levels of detectable dsRNA were produced by a genetically engineered cytopathogenic (cp) CSFV compared with ncp CSFV, and cp CSFV induced IFN-α/β in PK-15 cells. With DC, there was only a small difference in the levels of dsRNA between the cp and ncp viruses, and no IFN-α/β was produced. However, the cp virus induced a higher degree of DC maturation, in terms of CD80/86 and MHC II expression. N pro deletion mutants induced an increase in DC maturation and IFN-α/β production–for both ncp and cp viruses–despite reduced replication efficiency in the DC. Deletion of N pro did not influence dsRNA levels, indicating that the interference was downstream of dsRNA turnover regulation. In conclusion, the capacity of CSFV to replicate in myeloid DC, and prevent IFN-α/β induction and DC maturation, requires both regulated dsRNA levels and the presence of viral N pro.