Vpu Protein: The Viroporin Encoded by HIV-1

Abstract

Viral protein U (Vpu) is a lentiviral viroporin encoded by human immunodeficiency virus type 1 (HIV-1) and some simian immunodeficiency virus (SIV) strains. This small protein of 81 amino acids contains a single transmembrane domain that allows for supramolecular organization via homoligomerization or interaction with other proteins. The topology and trafficking of Vpu through subcellular compartments result in pleiotropic effects in host cells. Notwithstanding the high variability of its amino acid sequence, the functionality of Vpu is well conserved in pandemic virus isolates. This review outlines our current knowledge on the interactions of Vpu with the host cell. The regulation of cellular physiology by Vpu and the validity of this viroporin as a therapeutic target are also discussed.

Keywords: HIV-1; Viroporin; Vpu; antiretroviral target; ion transport; membrane permeability; membrane pore; protein trafficking.

Figure 1

Sequence and structure requirements for Viral protein U (Vpu) functionality. Vpu from the HXB2 strain is the reference amino acid sequence showing conserved amino acid (red), motifs (boxes), structural domains, and predicted helices. Numbers refer to amino acid positions. Table summarizes the consensus published data of each function. Each function was separately characterized, using different approaches. Further coordinated studies are needed to compare requirements of these functions.

Figure 2

Subcellular localizations of Vpu protein. Vpu modifies the protein transport of newly synthesized proteins. Degradation through the lysosome pathway (illustrated with Bone Marrow Stromal Cell Antigen 2 (BST2)) or the proteasome pathway (illustrated with CD4) are included. β-transducing-repeat-containing protein (βTrCP) or unknown cellular cofactor and also the two possible locations (trans-Golgi network (TGN) and plasma membrane (PM)) where BST2 and Vpu converge and traffic are depicted.