Viroporins

Viroporins Viroporins are virus-encoded proteins that participate in virus replication, including the promotion of release of virus particles from cells (Viroporins. FEBS Lett 2003 552: 28-34). They also affect cellular functions, including the cell vesicle system, glycoprotein trafficking and membrane permeability. Viroporins are usually not essential for the replication of viruses, but their presence enhances virus growth. Composed of 60-120 amino acids, viroporins have a hydrophobic transmembrane domain that interacts with lipid bilayers, and polymerization of viroporin monomers creates hydrophilic pores in the membranes of virus-infected cells. Viroporins are present in tiny amounts in the virus particles (virions) of many animal RNA viruses, e.g. influenza A virus M2 protein, poliovirus 2B and 3A proteins, HIV Vpu and SARS coronavirus E protein. Viroporins contribute to the pathology of virus diseases by altering membrane permeability and disrupting ion homeostasis in infected cells.

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A paper recently published in Cellular Microbiology reports that viroporins of hepatitis C virus, poliovirus and other animal RNA viruses induce apoptosis in host cells (Viroporins from RNA viruses induce caspase-dependent apoptosis. 2008 Cell Microbiol 10: 437-451). In addition to their capacity to disrupt ionic cellular homeostasis and promote cell lysis, the expressed viroporins were able to induce cell death. Degradation of DNA and generation of apoptotic bodies were observed on viroporin expression. Activation of caspase-3, altered mitochondrial morphology and detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin-induced apoptosis and shows that viroporins induce caspase-dependent programmed cell death.

It is possible that viroporins have different effects depending on the level of expression and/or the host-cell type. The induction of apoptosis in host cells by viruses is common and could assist virus spread. The next step in understanding the links between viroporins and apoptosis will be to unravel the mechanisms by which viroporins trigger apoptotic pathways and to demonstrate that these findings are relevant during virus infections.

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