Abstract
BackgroundHIV-1 mediated perturbation of the plasma membrane can produce an alteration in the transmembrane gradients of cations and other small molecules leading to cell death. Several HIV-1 proteins have been shown to perturb membrane permeability and ion transport. Xenopus laevis oocytes have few functional endogenous ion channels, and have proven useful as a system to examine direct effects of exogenously added proteins on ion transport.ResultsHIV-1 Nef induces alterations in the intracellular potassium concentration in CD4+ T-lymphoblastoid cells, but not intracellular pH. Two electrode voltage-clamp recording was used to determine that Nef did not form ion channel-like pores in Xenopus oocytes.ConclusionThese results suggest that HIV-1 Nef regulates intracellular ion concentrations indirectly, and may interact with membrane proteins such as ion channels to modify their electrical properties.
Highlights
During primary infection by HIV-1 or simian immunodeficiency virus (SIV) there is a rapid and nearly complete depletion of the mucosal CD4+ T cell population [1]
Direct HIV-1 mediated cell killing appears to be a major factor in both phases of CD4+ T-lymphocyte loss in AIDS or simian AIDS (SAIDS), immune dysregulation and other factors contribute [3,4]
HIV-1 mediated perturbation of the cellular membranes can produce an alteration in the transmembrane gradients of cations and other small molecules leading to cell death by lysis, cell-cell fusion, apoptosis and necrosis [8,9,10]
Summary
During primary infection by HIV-1 or simian immunodeficiency virus (SIV) there is a rapid and nearly complete depletion of the mucosal CD4+ T cell population [1]. This initial phase is followed by a prolonged phase in which there is a gradual decline in the overall numbers of peripheral CD4+ T cells, which appears to reflect accelerated rates of cell death and replacement [2]. HIV-1 mediated perturbation of the cellular membranes can produce an alteration in the transmembrane gradients of cations and other small molecules leading to cell death by lysis, cell-cell fusion, apoptosis and necrosis [8,9,10]. HIV-1 mediated perturbation of the plasma membrane can produce an alteration in the transmembrane gradients of cations and other small molecules leading to cell death. Xenopus laevis oocytes have few functional endogenous ion channels, and have proven useful as a system to examine direct effects of exogenously added proteins on ion transport
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