The core protein of a pestivirus protects the incoming virus against IFN-induced effectors

A multitude of viral factors - either inhibiting the induction of the IFN-system or its effectors – have been described to date. However, little is known about the role of structural components of the incoming virus particle in protecting against IFN-induced antiviral factors during or immediately after entry. In this study, we take advantage of the previously reported property of Classical swine fever virus (family Flaviviridae, genus Pestivirus) to tolerate a deletion of the core protein if a compensatory mutation is present in the NS3-helicase-domain (Vp447(∆c)). In contrast to the parental virus (Vp447), which causes a hemorrhagic-fever-like disease in pigs, Vp447(∆c) is avirulent in vivo. In comparison to Vp447, growth of Vp447(∆c) in primary porcine cells and IFN-treated porcine cell lines was reduced >20-fold. Also, primary porcine endothelial cells and IFN-pretreated porcine cell lines were 8–24 times less susceptible to Vp447(∆c). This reduction of susceptibility could be partially reversed by loading Vp447(∆c) particles with different levels of core protein. In contrast, expression of core protein in the recipient cell did not have any beneficial effect. Therefore, a protective effect of core protein in the incoming virus particle against the products of IFN-stimulated genes could be demonstrated.