Membrane potential depolarization as a triggering mechanism for Vpu-mediated HIV-1 release

Biophys J. 2010 Sep 22;99(6):1718-25. doi: 10.1016/j.bpj.2010.07.027.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Polarity
  • Gene Knockdown Techniques
  • HIV-1 / metabolism
  • HIV-1 / physiology*
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Humans
  • Membrane Potentials*
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Point Mutation
  • Potassium Channels, Tandem Pore Domain / deficiency
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism
  • Viral Regulatory and Accessory Proteins / metabolism*
  • Virus Release*


  • Human Immunodeficiency Virus Proteins
  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1
  • potassium channel subfamily K member 3