1.A.40 The Human Immunodeficiency Virus Type I, HIV-1 (Retrovirdiac) Vpu Channel (Vpu-C) Family

The Vpu-C channel protein is expressed in the subcellular membranes of infected cells but not in the membrane envelope of the virion. It plays multiple roles in the life cycle of HIV-1: it triggers virus release, probably dependent on channel formation, and it binds residues 402-420 of CD4 of the host cell. CD4 is the virion receptor for HIV-1, and Vpu promotes CD4 degradation. It is an 81 aa type I membrane protein, phosphorylated on serine residues 52 and 56. It forms a homopentameric channel, but can form multiple oligomers. Its channel activity has been reconstituted in planar lipid bilayers. It is a general ion conducting channel that prefers monovalent cations over anions.

Synthetic proteins with 4 or 5 TMSs, all derived from the TMS of Vpu, have been constructed (Becker et al., 2004). They form discrete ion channels with conductances of 42 and 76 pS, respectively. This suggests that self assembly of monomers forms the physiological channel, most likely a pentamer.

Although it is clear that Vpu can form channels, it is not certain that Vpu-mediated channel formation is the mechanism by which it exerts its physiological function. Vpu and the N-terminal 40 residue region of the mammalian background K⁺ channel, TASK-1, have structural and functional similarity, and these two proteins physically interact (Hsu et al., 2004). Vpu abolished the TASK-1 current, and overexpression of TASK-1 led to impairment of Vpu's ability to enhance viral particle release. Thus, it is possible that Vpu, a multifunctional protein, functions to control the current of TASK-1.

The generalized transport reaction catalyzed by Vpu is:

ions (in) ions (out)