University of Cambridge > > Departmental Seminar Programme, Department of Veterinary Medicine > Role of Ca2+ in rotavirus entry, assembly and the pathogenesis of diarrhoea

Role of Ca2+ in rotavirus entry, assembly and the pathogenesis of diarrhoea

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Ca2+ plays a key role in many pathological processes, including viral infections. Rotavirus, the major etiological agent of viral gastroenteritis in children and young animals, provides a useful model to study a number of Ca2+ dependent virus-cell interactions. Rotavirus entry, activation of transcription, morphogenesis, cell lysis and particle release are Ca2+-dependent processes. In the extracellular medium, Ca2+ stabilizes the structure of the viral capsid formed by three concentric protein layers. The mechanism by which rotavirus and other nonenveloped viruses enter the cell is still not clear. We have proposed an endocytosis model where the critical step for virus uncoating and membrane permeabilization is the decrease in Ca2+concentration in the endosome. Low Ca2+ in the endosome would induce solubilization of coat proteins and permeabilization of the vesicle to release double layer particles (DLP) in the cytoplasm and activate transcriptase. Newly form DLP bud into the ER for the acquisition of the capsid outer layer and requires a high Ca2+ concentration inside this compartment. Infection modifies Ca2+ homeostasis of the cell, increasing plasma membrane Ca2+ permeability leading to elevation of [Ca2+]i, and ER Ca2+ content, which may be advantageous to virus replication. These changes have been associated to the expression of the glycosylated nonstructural viral protein NSP4 . The mechanisms involved in Ca2+ entry are unknown, but NSP4 may act as a viroporin and/or activate the Na+/Ca2+ exchanger (NCX) operating in the reverse mode. An elevated Ca2+ concentration induces cell dysfunction and, eventually, cell death. The role of these changes in the production of diarrhoea will be discussed.

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

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