Proton Permeability of HIV Virus like Particles and Vesicular Stomatitis Virus

Abstract

Enveloped viruses have been assumed to be impermeable to protons around neutral pH. Here we report the permeability of bald as well as VSV G pseudotyped HIV virus like particles (VLPs) in their mature and immature states as well as wild type VSV virions. Permeability was measured on single isolated virions incorporating pHlorins by changing the external PH from neutral pH to 6.2. pHlorin's fluorescence depends on their protonation state with a pKa of 7.18. We found all HIV VLPs and VSV virions to be permeable to protons, with fast permeation due to nanopore formation at the initial phase followed by the diffusion of protons across the membrane. Maturation of the HIV VLPs increased the permeation rate by a factor of two suggesting the Gag lattice lowers the permeability of immature VLPs. The average permeation rate of the VSV virions as well as HIV VLPs was similar to the previously measured rate for 150 nm lipid vesicles and all virions equilibrated to the outside pH well below 10 min after being subjected to pH 6.2. Our data suggests that permeation of envelopes within VSV virions and HIV VLPs is governed through the same permeation mechanism as lipid vesicles with similar sizes and none of the virions in this study are impermeable, at least if one can wait a sufficiently long time.