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

Sze, Ching Wooen; Tan, Yee-Joo

Another cell death pathway that is often activated during an insult is autophagy. Autophagy occurs through the intracellular membrane trafficking system by delivering damaged or unwanted cellular material from the cytosol to the lysosome for degradation, and thus can be referred to as "self-eating" [165] . During autophagy, cellular components are sequestered into a double-membrane vesicle termed an autophagosome, which then fuses with a lysosome where degradation can occur [166, 167] . Viruses have evolved to manipulate and interfere with different stages of this destructive process to their benefit. For instance, M2 is able to inhibit the fusion between autophagosome and lysosome independent of its proton channel activity by interacting with the autophagy-related protein, Atg6/Beclin-1 [162, 168, 169] . By doing so, degradation of the autophagosomes is inhibited, leading to accumulation of these vesicles in the infected cells. Some viral infections can induce autophagy-related vesicles' formation so they can be subverted to the viruses' advantage. During poliovirus infection, formation of autophagy-like double-membrane vesicles is induced by 2BC and 3A viral proteins [170] [171] [172] . The 3A viroporin then further inhibits the movement of these vesicles along the microtubules and blocks the maturation and degradation of these vesicles to benefit the viral growth and release [173, 174] . For rotavirus infection, autophagy is induced when NSP4 permeabilizes the ER membrane and releases the calcium storage into the cytoplasm. A sudden surge in cytoplasmic calcium concentration activates the calcium-dependent autophagy pathway, which is then tricked into transporting the viral proteins from the ER to the viroplasm for replication and assembly [42, 43, 114] .