Membrane Potential Depolarization as a Triggering Mechanism for Vpu-Mediated HIV-1 Release

作者:Hsu Kate*; Han Jin; Shinlapawittayatorn Krekwit; Deschenes Isabelle; Marban Eduardo
来源:Biophysical Journal, 2010, 99(6): 1718-1725.
DOI:10.1016/j.bpj.2010.07.027

摘要

Vpu, a component unique to HIV-1, greatly enhances the efficiency of viral particle release by unclear mechanisms. This Vpu function is intrinsically linked to its channel-like structure, which enables it to interfere with homologous transmembrane structures in infected cells. Because Vpu interacts destructively with host background K(+) channels that set the cell resting potential, we hypothesized that Vpu might trigger viral release by destabilizing the electric field across a budding membrane. Here, we found that the efficiency of Vpu-mediated viral release is inversely correlated with membrane potential polarization. By inhibiting the background K(+) currents, Vpu dissipates the voltage constraint on viral particle discharge. As a proof of concept, we show that HIV-1 release can be accelerated by externally imposed depolarization alone. Our findings identify the trigger of Vpu-mediated release as a manifestation of the general principle of depolarization-stimulated exocytosis.

  • 出版日期2010-9-22