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

Sze, Ching Wooen; Tan, Yee-Joo

Besides acting as an ion channel, viroporin can have important roles that are independent of its pore-forming and ion-conducting abilities. Recent data have provided strong evidence for defining the role of p7 in the viral life cycle of HCV. The assembly of HCV viral particles commences in the cellular organelle termed the lipid droplets (LD) [132] (see recent review [133] for a detailed overview of the HCV life cycle). During the viral assembly process, LD is proposed to serve as a platform for viral assembly by concentrating the viral capsid core protein in close proximity to the replication complex located in the ER membranes [134, 135] . p7 has been shown to interact with three other HCV structural proteins, including the core protein and two other glycoproteins E1 and E2 [136] . A study by Gentzsch et al. showed that mutations in the p7 cytoplasmic loop led to retention of core in the LD and subsequent defects in virus production [26] . Besides interaction with the structural proteins, p7 can also affect the processing of the viral polyprotein between E2/p7 and p7/NS2; without it there is defective virus production [27,137]. Another important role that p7 has in the HCV life cycle is manipulating the distribution of the non-structural protein NS2 and influencing the interactions between NS2 and other viral proteins to coordinate the assembly process, independent of its ion channel activity [24, 25, 137] . All these imply that in addition to its calcium channel activity [138] , p7 plays an important part in the morphogenesis of the HCV virion. Thus it is of no surprise that p7 has emerged as the target of antiviral therapy for HCV. Several p7 inhibitors have been found, such as the M2 inhibitor amantadine, and iminosugars, and the hunt for more inhibitors is still actively pursued [74, 76, 139, 140 ].