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

Sze, Ching Wooen; Tan, Yee-Joo

The Vpu viroporin is only present in HIV-1 and absent from the type 2 HIV virus genome [92] . Vpu is a selective ion channel [93] that is believed to play two main functions in the viral life cycle. The cytoplasmic domain is responsible for the interaction with and degradation of CD4 while the TMD plays a role at the viral release stage, which will be discussed in the following section. During viral replication, the Env glycoprotein forms a stable complex with the cellular CD4 molecule in the ER, thus preventing the trafficking of both Env and CD4 to the cell surface [66] [67] [68] [94] [95] [96] . The cytoplasmic domain of Vpu can physically bind CD4 [97] [98] [99] and induce its degradation [17] [18] [19] [20] . This induction is dependent on the phosphorylation of two key residues, Ser52 and Ser56 in the cytoplasmic region of Vpu [100, 101] . A key residue located in the TMD of Vpu, Trp22, though not required for the interaction between Vpu and CD4, is crucial for the targeting of CD4 to the ER-associated degradation pathway (ERAD) [102] . In the absence of Vpu, CD4 molecules are incorporated into the HIV-1 particles, causing the formation of glycoprotein gp120-CD4 complexes and reducing the level of functional Env glycoproteins on the virion surface [21] .