Viroporins: structure and biological functions

Key Points

• 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, Ca ²⁺ 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.

Abstract

Viroporins belong to a growing family of virally encoded proteins that form aqueous channels in the membranes of host cells. Here, Carrasco and colleagues review the structure and diverse biological functions of these proteins during the viral life cycle, as well as their potential as antiviral therapeutic targets.

Abstract

Viroporins are small, hydrophobic proteins that are encoded by a wide range of clinically relevant animal viruses. When these proteins oligomerize in host cell membranes, they form hydrophilic pores that disrupt a number of physiological properties of the cell. Viroporins are crucial for viral pathogenicity owing to their involvement in several diverse steps of the viral life cycle. Thus, these viral proteins, which include influenza A virus matrix protein 2 (M2), HIV-1 viral protein U (Vpu) and hepatitis C virus p7, represent ideal targets for therapeutic intervention, and several compounds that block their pore-forming activity have been identified. Here, we review recent studies in the field that have advanced our knowledge of the structure and function of this expanding family of viral proteins.