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

Sze, Ching Wooen; Tan, Yee-Joo

During an active infection, a virus hijacks the host molecular machinery and turns it into a virus factory. When the ion channel activity of viroporin is activated during viral infection, perturbation of the host membrane permeability occurs, leading to disruption of the cellular ion homeostasis and subsequent cytophatic events. Many viroporins are expressed as ER proteins and remained localized to the ER during virus replication, while several have been shown to be partially localized to the mitochondria [155] [156] [157] . The ER serves as the organelle that stores a major portion of the cell's calcium ion where a >1000-fold gradient is maintained across the ER membrane and the cytoplasm [40, 158] . Expression of viral ion channels at the ER membrane causes leakage of Ca 2+ from the ER storage into the cytoplasm (see review [40] ). Fluctuation of the cytosolic Ca 2+ concentration can inhibit protein trafficking through TGN and inhibit antiviral response, as mentioned in the previous section. It can also trigger several defensive signaling pathways, including apoptosis, autophagy, and inflammasome formation, in an attempt to contain and eliminate the invader. However, viruses have evolved to adapt and subvert these defense mechanisms for their own growth benefits. The strategy involved and how these antiviral pathways become pro-viral growth are only beginning to be explored.