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Published on: December 16, 2019
Changes in blood cell membrane properties in HIV type-1-infected patients
J Martins-Silva1, Nuno C Santos, M Doroana
1Instituto de Biopatologia Química/Faculdade de Medicina de Lisboa and Unidade de Biopatologia Vascular/Instituto de Medicina Molecular, 1649-028 Lisboa, Portugal.
Insights
Human Immunodeficiency Virus type 1 (HIV-1) infection alters cell membranes and calcium signaling in lymphocytes and erythrocytes. These changes in membrane fluidity and acetylcholinesterase activity may facilitate viral spread and production.
Area of Science:
- Virology
- Cell Biology
- Biophysics
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) infection is known to affect cellular functions.
- Understanding HIV-1's impact on cell membranes and calcium signaling is crucial for comprehending viral pathogenesis.
Purpose of the Study:
- To investigate HIV-1 infection-induced alterations in cell membrane properties and calcium signaling.
- To evaluate changes in membrane fluidity, acetylcholinesterase (AChE) activity, and intracellular calcium concentration ([Ca2(+)](int)) in lymphocytes and erythrocytes of untreated HIV-1-infected individuals.
Main Methods:
- Membrane fluidity was measured using fluorescence spectroscopy with DPH and TMA-DPH probes.
- Acetylcholinesterase (AChE) activity was determined using Ellman's colorimetric method.
- Intracellular calcium concentration ([Ca2(+)](int)) was assessed using the fluorescent indicator fura-2 acetoxymethyl ester.
Main Results:
- Lymphocytes from HIV-1 infected individuals showed decreased membrane fluidity, reduced AChE activity, and increased [Ca2(+)](int) compared to controls.
- Erythrocytes from HIV-1 infected individuals exhibited decreased [Ca2(+)](int) and reduced membrane fluidity near the lipid/water interface.
- Significant biochemical and biophysical changes were observed in both lymphocytes and erythrocytes due to HIV-1 infection.
Conclusions:
- HIV-1 infection induces substantial changes in cell membrane properties and membrane protein activity in lymphocytes and erythrocytes.
- These observed alterations may contribute to the facilitated propagation of HIV-1 infection, enhanced virion production, and the establishment of infectious viral reservoirs.
Abstract:
To evaluate the possible HIV-1 infection-induced changes in cell membrane properties and in calcium signaling, membrane fluidity, acetylcholinesterase (AChE, a glycosylphosphatidylinositol-anchored protein) activity, and intracellular calcium concentration ([Ca2(+)](int)) were evaluated in lymphocytes and erythrocytes of infected individuals, previous to their engagement in antiretroviral therapy. Membrane fluidity was assessed by fluorescence spectroscopy measurements, using the fluorescence probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). AChE activity was determined by the colorimetric Ellman's method and [Ca2(+)](int) using the fluorescent fura-2 acetoxymethyl ester. When compared with the control group, lymphocytes of infected patients presented significantly decreased membrane fluidity, decreased AChE activity, and increased [Ca2(+)](int). Erythrocytes from HIV-infected patients presented decreased [Ca2(+)](int) when compared with the control group and decreased membrane fluidity near the lipid/water interface. Our data show that HIV-1 infection leads to biochemical and biophysical changes in the membrane itself and in membrane protein activity in lymphocytes (average of infected and noninfected subpopulations) and even in erythrocytes. The present observations are in agreement with a process of facilitated propagation of the infection to new cells, stimulation of virion production, and maintenance of a reservoir of erythrocyte-bound infectious virus.
