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Chapter 11 : Remodeling Cellular Membranes
Category: Viruses and Viral Pathogenesis
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The extensive cellular membrane remodeling exerts major effects on cellular metabolic and physiologic functions, which may be important for viral suppression of antiviral responses within the infected host. This chapter describes the current status of our understanding of the induction and formation of membranous viral RNA replication sites for the different picornaviruses. Picornaviruses replicate their genomes in close association with cellular membranes. Fractionation of cytoplasmic extracts from infected cells demonstrated that viral RNA replication activity was associated with these new structures. Subsequently, improved imaging technology greatly increased our knowledge of the morphological changes occurring in cells infected with poliovirus as well as other members of the Picornaviridae family. Picornavirus 3A proteins show a variable size, ranging from 73 to 153 aa. They all contain at least one hydrophobic domain, which most likely serves to anchor the protein in the vesicles at which viral RNA replication takes place. Parechovirus and foot-and-mouth disease virus (FMDV) proteins interact with early secretory pathway membranes, but none of them interacts with GBF1 or interferes with membrane traffic or perturbs the secretory pathway organelle structure. We are now only beginning to understand the details of the three-dimensional structures that ultimately comprise the viral RNA replication complexes and the interactions of viral and cellular factors that lead to the dramatic remodeling of cellular membranes to form these structures. The Picornaviridae are a diverse group of viruses that infect a wide range of hosts; they are responsible for a broad spectrum of disease patterns.
Thin-section electron micrograph of a HeLa cell infected with the Mahoney strain of poliovirus type 1 for 4 h. The cells were fixed and then processed for electron microscopy.
Three-dimensional surface-rendered model of replication complexes observed in poliovirus-infected HeLa cells at 4 h postinfection. Electron tomography was performed on a selected region from a 200-nm-thick section of an infected cell. The model was generated from a tilt series of images digitally processed to produce the reconstruction.