Chapter 20 : Role of Cellular Structures in Viral RNA Replication

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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.

Citation: Egger D, Gosert R, Bienz K. 2002. Role of Cellular Structures in Viral RNA Replication, p 247-253. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch20
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Image of FIGURE 1

Morphology of and viral RNA synthesis in PV-infected HEp-2 cells, (a) Electron microscopic picture shows a large field of polioviral vesicles. Bar, 1 m. (b) Giemsa-stained cells in the LM, the large cytoplasmic eosinophilic inclusion (*) corresponds to the vesiculated area in Fig. 1a . Bar, 10 m. (c) High-resolution autoradiograph, silver grains indicate incorporation of H-uridin into viral RNA on the surface of PV vesicles. Bar, 100 nm.

Citation: Egger D, Gosert R, Bienz K. 2002. Role of Cellular Structures in Viral RNA Replication, p 247-253. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch20
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Image of FIGURE 2

An isolated, native replication complex appears as a rosette-like structure. Tubules of the vesicles point toward the center of the rosette. Immunogold labeling for PV proteins 2B and 2C and precursors. Bar, 100 nm.

Citation: Egger D, Gosert R, Bienz K. 2002. Role of Cellular Structures in Viral RNA Replication, p 247-253. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch20
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