EFFECTS OF VPU EXPRESSION ON XENOPUS OOCYTE MEMBRANE CONDUCTANCE

The HIV-l-specific vpu gene encodes an integral membrane phosphoprotei n which affects three aspects of the HIV-I infectious cycle: it enhanc es virion release from infected cells; it causes degradation of the CD 4 protein in the endoplasmic reticulum; and it delays syncytia formati on in HIV-l-infected CD4(+) T-cells. Although little is known about ho w Vpu mediates these effects, it has been proposed to function as a no nspecific cation channel, In this report, voltage clamp measurements o f Xenopus oocytes show that Vpu expression is not associated with incr eased transmembrane currents. Instead, Vpu expression diminishes membr ane conductance. Injection of 4.6 ng of Vpu mRNA into these cells redu ces endogenous potassium conductance by 50%. Only Vpu mutants which re tain the ability to degrade CD4 can diminish K+ conductance. Inhibitio n by Vpu is not unique to K+ channels as it is also observed on severa l coexpressed membrane proteins but not on a coexpressed cytoplasmic p rotein. These results indicate that the CD4 degradative capability of Vpu and the Vpu-mediated modulation of membrane protein expression are mechanistically coupled and that Vpu may contribute to HIV pathogenes is by altering plasma membrane protein expression at the cell surface, (C) 1998 Academic Press.