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| - Virus encoded ion channels, termed viroporins, are expressed by a diverse set of viruses and have been found to target nearly every host cell membrane and compartment, including endocytic/exocytic vesicles, ER, mitochondria, Golgi, and the plasma membrane. Viroporins are generally very small (<100 amino acids) integral membrane proteins that share common structure motifs (conserved cluster of basic residues adjacent to an amphipathic alpha-helix) but only limited sequence homology between viruses. Ion channel activity of viroporins is either required for replication or greatly enhances replication and pathogenesis. Channel characteristics have been investigated using standard electrophysiological techniques, including planar lipid bilayer, liposome patch clamp or whole-cell voltage clamp. In general, viroporins are voltage-independent non-specific monovalent cation channels, with the exception of the influenza A virus M2 channel that forms a highly specific proton channel due to a conserved HXXXW motif. Viroporin channel currents range between highly variable (‘burst-like’) fluctuations to well resolved unitary (‘square-top’) transitions, and emerging data indicates the quality of channel activity is influenced by many factors, including viroporin synthesis/solubilization, the lipid environment and the ionic composition of the buffers, as well as intrinsic differences between the viroporins themselves. Compounds that block viroporin channel activity are effective antiviral drugs both in vitro and in vivo. Surprisingly distinct viroporins are inhibited by the same compounds (e.g., amantadines and amiloride derivatives), despite wide sequence divergence, raising the possibility of broadly acting antiviral drugs that target viroporins. Electrophysiology of viroporins will continue to play a critical role in elucidating the functional roles viroporins play in pathogenesis and to develop new drugs to combat viroporin-encoding pathogens.
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