In the complex interaction between virus and cell, plasma and intracellular membranes represent a physical barrier whose integrity must be altered during specific steps of viral cycle.  To achieve this goal, viruses code for specific proteins which modulate membrane permeability by mechanisms which are similar to other known ion channel proteins.

Ion channel are integral membrane proteins that allow passive flux of inorganic ions through a central pore.  Among the channel proteins of viral origin, M2 of influenza virus has been extensively characterized.  This protein associated into an active homotetramer which allows protons to enter viral particle during the uncoating in endosomes.  Each subunit of the tetramer presents a single transmembrane hydrophobic domain which forms the pore of the channel.  The E1 protein of HCV shares with M2 the ability to alter membrane permeability.  In our studies, we demonstrated that expression of E1 in E. coli alters the permeability of membrane and induces cell dealth as a consequence of membrane damage.  The hydrophobic region localized at the C-terminal end of E1 is an important domain for the interaction with membrane and is mainly responsible for the permeability changes and the lytic effect induced by E1 protein.  A second internal hydrophobic region which may cooperate with C-terminal one has also been identified suggesting that E1 could interact with the membrane through a more complex mechanism involving multiple regions.  All these finding indicate that E1 can be consider as a new component of a family of membrane proteins encoded by RNA viruses.  These proteins act by affecting membrane integrity and can be involved in different steps of viral cycle like cell lysis, membrane fusion and alteration of intracellular ionic composition.