Viroporins: structure and biological functions

Viroporins are small virally encoded hydrophobic proteins that oligomerize in the membrane of host cells, leading to the formation of hydrophilic pores. This activity modifies several cellular functions, including membrane permeability, Ca2+ homeostasis, membrane remodelling and glycoprotein trafficking.A classification scheme for viroporins is proposed on the basis of their structure and membrane topology. Thus, class I and class II viroporins are defined according to the number of transmembrane domains in the protein (one and two, respectively), and subclasses are defined according to their orientation in the membrane.The main function of viroporins during viral replication is to participate in virion morphogenesis and release from host cells. In addition, some viroporins are involved in viral entry and genome replication.The structure and activity of several viroporins, such as picornavirus protein 2B (P2B), influenza A virus matrix protein 2 (M2), hepatitis C virus p7 and HIV-1 viral protein U (Vpu), have been analysed in detail.New members of this expanding family of viral proteins have been described, from both RNA and DNA viruses. In addition to having a common general structure, all of these new viroporins have the ability to increase membrane permeability.Viroporins represent ideal targets to block viral replication and the spread of infection. Although a number of selective inhibitors of viroporin ion channels have been analysed in detail, optimized screening systems promise to provide new and more potent antiviral compounds in the near future.