Membrane potential depolarization as a triggering mechanism for Vpu-mediated HIV-1 release.
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.
Hsu
Kate
K
Department of Medical Research, Mackay Memorial Hospital, Tamsui, Taiwan. khsu1@ms1.mmh.org.tw
Han
Jin
J
Shinlapawittayatorn
Krekwit
K
Deschenes
Isabelle
I
Marbán
Eduardo
E
D001483:Base Sequence; D016764:Cell Polarity; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D057074:Virus Release; D000086082:Viroporin Proteins
D054298:Human Immunodeficiency Virus Proteins; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C420132:potassium channel subfamily K member 3