Cell surface effects of human immunodeficiency virus

Increases in intracellular concentrations of potassium ([K ؉ ] i ) and sodium ([Na ؉ ] i ) occur concomitantly with cytopathic effects induced in a CD4 ؉ T-lymphoblastoid cell line acutely infected by human immunodeficiency virus (HIV). This [K ؉ ] i increase was greater in cells infected by cytopathic HIV strains than in cells infected by less cytopathic strains. T cells persistently infected by HIV had an increased [K ؉ ] i but displayed an [Na ؉ ] i similar to that of mock-infected cells. HIV induced increases in [K ؉ ] i and [Na ؉ ] i after cytopathic infection of human peripheral blood mononuclear cells, but the magnitude of the Na؉ changes did not correlate with the extent of the cytopathic effect. Enhanced movement of cations may osmotically drive water entry, resulting in balloon degeneration and lysis of HIV-infected cells. These observations offer potential approaches for antiviral therapies.

supporting

confidence: 71%

Section: True-color-real-time Microscopic Analysis Of Hiv-infected Anmentioning

confidence: 99%

Alteration of intracellular potassium and sodium concentrations correlates with induction of cytopathic effects by human immunodeficiency virus

Voss

Fermin

Levy

et al. 1996

“…The mechanism by which HIV reduces pH i in T-lymphoblastoid cells is not established in the current study. Prior studies indicated that HIV infection increases [Na ϩ i ] (20,54). Homeostatic mechanisms that control pH i may respond to the increase in [Na ϩ ] i by reducing the activity of the Na ϩ /H ϩ exchange system.…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus infection of T-lymphoblastoid cells reduces intracellular pH

Makutonina

Voss

Plymale

et al. 1996

Alterations in plasma membrane function are induced by many cytopathic viruses, including human immunodeficiency virus type 1 (HIV-1). These alterations can result in changes in the intracellular content of ions and other small molecules and can contribute to cytolysis and death of the infected cell. The pH-sensitive fluorescent probe 2,7-bis(2-carboxyethyl)-5,6-carboxyfluorescein-acetoxymethyl ester was used to quantitate intracellular pH (pH i ) in HIV-1-infected T cells. Infection of cells from the CD4 ؉ T-lymphoblastoid line HUT-78 (RH9 subclone) with HIV-1 strain LAI resulted in a significant decrease of pH i , from approximately 7.2 in mock-infected cells to below 6.7 by day 4 after infection, when cells were undergoing acute cytopathic effects. The pH i in persistently infected cells that survived the acute cytopathic effects of HIV-1 was approximately 6.8 to 7.0. Studies with amiloride, an inhibitor of the Na ؉ /H ؉ exchange system, suggest that HIV-1induced intracellular acidification in lymphocytes is due, in part, to dysfunction of this plasma membrane ion transport system. The alterations in pH i may mediate certain cytopathic effects of HIV-1, thereby contributing to depletion of CD4 ؉ T lymphocytes in patients with AIDS.

“…Thus, syncytium formation is the consequence of increased cell fusion, an activity related to the virus glycoprotein gp41 (7,25,42,44). The mechanisms of individual cell killing are more complex; several HIV-1 gene products, such as gp41 and Vpu, could participate in this process by inducing plasma membrane modifications (16,28). Thus, permeability of membranes to a number of compounds, including ions, increases in HIV-1infected T cells, suggesting the appearance of hydrophilic pores in the membrane (40) as occurs in other virus-cell systems (10).…”

mentioning

confidence: 99%

Membrane permeabilization by different regions of the human immunodeficiency virus type 1 transmembrane glycoprotein gp41

Arroyo

Boceta

González

et al. 1995

The transmembrane glycoprotein (gp41) of human immunodeficiency virus type 1 (HIV-1) has been implicated in the cytopathology observed during HIV infection. The first amino acids located at the amino terminus are involved in membrane fusion and syncytium formation, while sequences located at the carboxy terminus have been predicted to interact with membranes and modify membrane permeability. The HIV-1 gp41 gene has been cloned and expressed in Escherichia coli cells by using pET vectors to analyze changes in membrane permeability produced by this protein. This system is well suited for expressing toxic genes in an inducible manner and for analyzing the function of proteins that modify membrane permeability. gp41 enhances the permeability of the bacterial membrane to hygromycin B despite the low level of expression of this protein. To localize the regions of gp41 responsible for these effects, a number of fragments spanning different portions of gp41 were inducibly expressed in E. coli. Two regions of gp41 were shown to increase membrane permeability: one located at the carboxy terminus, where two highly amphipathic helices have been predicted, and another one corresponding to the membrane-spanning domain. Expression of the central region of gp41 comprising this domain was highly lytic for E. coli cells and increased membrane permeability to a number of compounds. These findings are discussed in the light of HIV-induced cytopathology and gp41 structure.