THE VPU PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FORMS CATION-SELECTIVE ION CHANNELS

Vpu is a small phosphorylated integral membrane protein encoded by the human immunodeficiency virus type 1 genome and found in the endoplasm ic reticulum and Golgi membranes of infected cells, It has been linked to roles in virus particle budding and degradation of CD4 in the endo plasmic reticulum. However, the molecular mechanisms employed by Vpu i n performance of these functions are unknown. Structural similarities between Vpu and the M2 protein of influenza A virus have raised the qu estion of whether tile two proteins are functionally analogous: M2 has been demonstrated to form cation-selective ion channels in phospholip id membranes, In this paper we provide evidence that Vpu, purified aft er expression in Escherichia coli, also forms ion channels in planar l ipid bilayers. The channels are approximately five- to sixfold more pe rmeable to sodium and potassium cations than to chloride or phosphate anions, A bacterial cross-feeding assay was used to demonstrate that V pu can also form sodium-permeable channels in vivo in the E. coli plas ma membrane.