ABSTRACT

A possible consequence of viral cell infection is an association of viral antigens with cellular proteins. We observed such an interaction between non-structural protein 3 (NS3) of hepatitis C virus (HCV) and the serine/threonine specific protein kinases: protein kinase C (PKC) and cAMP dependent protein kinase (PKA). A highly conserved arginine-rich sequence of NS3 located between amino acid residues 1487 and 1500 of the HCV polyprotein, that resembles the autoregulatory domain of both kinases, mediates the binding of the kinases to NS3 and the inhibition of their enzymatic activity. As a consequence of the interaction an inhibition of free shuttling of PKA and PKC between cell compartments or transport of smaller NS3 fragments with the translocating kinases upon their activation was observed.

In in vitro experiments a further biological active domain of NS3 located between amino acid residues 1343 and 1379 of the HCV polyprotein was defined and characterized. This domain mediates binding and conformational changes of core histones. The NS3- induced conformational changes alter the properties of the histones as substrates for PKC and PKA and affect their interactions with DNA.