Role of Cellular Structures in Viral RNA Replication

During their replication cycles many viruses extensively affect host cell morphology. Pathologists diagnosed viral diseases on the basis of morphological characteristics of the diseased tissue long before the nature and biology of vimses were known. The take-off of modern experimental virology was the observation by Enders that in cultured cells poliovims (PV) induces morphological alterations, termed cytopathic effect (CPE). Subsequently, CPE could be used as an easy marker for virus replication in cell cultures. Picornaviruses, with the possible exception of hepatitis A virus (HAV), induce cell alterations that culminate ultimately in cell death. Picornavirus-induced cell alterations and cell destruction are directly coupled to viral replication. This was also demonstrated in coxsackievirus-infected muscles of mice where viral RNA replication located to the foci of gradual destruction of the contractile material. Expression of individual viral proteins in HeLa cells also pointed to the viral protein 2BC as the protein responsible for triggering the vesicle formation process, possibly assisted by protein 3A. Recent experiments visualized the vesicle budding process at the ER and demonstrated that the formation of vesicles is part of the anterograde transport. For PV RNA replication, translation of an individual RNA molecule has to be down-regulated to allow for transcription. The proposed mechanism for this switch consists of an enhanced 3CD-mediated binding of the cellular poly(rC)-binding protein to the 5'-cloverleaf structure of plus-strand viral RNA.