Viral Membrane Channels: Role and Function in the Virus Life Cycle

Sze, Ching Wooen; Tan, Yee-Joo

For enveloped viruses, budding and scission are commonly used to release the virus from infected cells. The 6K viroporin of the alphavirus [141] appears to assist in viral release via direct insertion into the plasma membrane. Through insertion into the lipid bilayer, it is proposed that the interfacial domain of 6K can then disrupt the cohesion of the outer membrane phospholipid to prompt viral release [35, 37] . Deletion of the 6K gene, as well as mutational analysis of the conserved amino terminal region of 6K essential for its partitioning into the membrane, led to a defect in the budding of infectious particles [36, 37] , further supporting the role of viroporin in the release of alphavirus. In IAV, M2 can induce membrane fission using a conserved amphipathic domain within M2, residues 47-61, which bind cholesterol and induce membrane curvation, leading to invagination of the liposome membrane and subsequent pinching off of the membrane vesicles [15, 16] . Deletion of this region resulted in a defect in viral release where a phenotypic beads-on-a-string budding pattern is seen due to incomplete scission, further substantiating the direct role of M2 in virus budding [16, 142, 143] . In SARS-CoV, in addition to the E protein, a second viroporin, 3a, was identified [31]. Depletion of 3a using siRNA significantly suppresses the release of viral particles into the culture media [32] . However, the underlying molecular mechanism involved is yet to be determined.