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

Sze, Ching Wooen; Tan, Yee-Joo

In addition to targeting CD4 for degradation, the ion channel Vpu is also required for efficient release of HIV-1 virions from infected cells, where it assists in depolarizing the host membrane and thus disrupting the electrical barrier at the membrane to enhance the release of HIV-1 particles [23] . Similar to M2, different regions of Vpu can interact with different host factors and contribute to the viral pathogenesis [22, 144, 145] . For instance, the second alpha-helix within Vpu can interact with tetherin, targeting it for endosomal degradation to counteract its inhibitory effect on viral release [145] [146] [147] [148] [149] and at the same time suppressing the innate immune response to ensure a successful infection [150, 151] . A recent study also found that the binding of Vpu H2 α-helix within the cytoplasmic tail to tetherin is able to displace the latter from the viral assembly site at the cell surface in order to produce virions devoid of tetherin on the surface [152] . In the absence of a functional Vpu, mature virions accumulate in the endosomal compartments or remain attached to the cell surface by tetherin [146, 150, 153] . A crystal structure of a protein complex containing both Vpu-tetherin as well as the core of the clathrin adaptor protein complex 1 (AP1) was obtained recently and this opens up the possibility that Vpu may be able to modulate the fate of other host proteins by hijacking the clathrin-dependent trafficking pathways [154] .