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Updated: Aug 7, 2026
Single-Cell Characterization of Calcium Influx and HIV-1 Infection using a Multiparameter Optofluidic Platform
Published on: May 18, 2021
HIV infection of mononuclear cells is calcium-dependent
Joshua J Anzinger1, Isaac Mezo, Xin Ji
1Department of Immunology and Microbiology, Rush University Medical Center, 1735 W. Harrison St., Cohn Building, Chicago, IL 60612, USA.
Insights
Divalent cations like calcium are crucial for HIV attachment and infection of immune cells. Blocking these cations significantly inhibits viral entry, offering new prevention strategies.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Preventing initial human immunodeficiency virus (HIV) infection is a critical public health goal.
- Peripheral blood mononuclear cells (PBMCs) are key targets for HIV, encompassing CD4(+) T cells, monocytes, and dendritic cells.
Purpose of the Study:
- To investigate the role of divalent cations in HIV attachment to and infection of PBMCs.
- To identify cell-surface molecules involved in HIV binding.
Main Methods:
- Treatment of PBMCs with EDTA and EGTA to chelate divalent cations.
- Assessing HIV infection and binding levels after cation chelation.
- Investigating the effect of specific cations (Ca(2+), Mn(2+), Mg(2+)) on viral binding.
- Evaluating the impact of trypsin treatment, mannan, and soluble ICAM-1 on HIV attachment.
Main Results:
- EDTA reduced HIV infection of PBMCs by 92% and viral binding by over 85%.
- EGTA also inhibited HIV binding, with Ca(2+) or Mn(2+) fully restoring binding, but not Mg(2+).
- Trypsin treatment dose-dependently inhibited virus attachment, suggesting protein involvement, while mannan and soluble ICAM-1 had no effect.
Conclusions:
- A calcium-dependent cell-surface protein mediates the majority of HIV attachment to and infection of PBMCs.
- Understanding this interaction may lead to novel strategies for preventing HIV infection.
Abstract:
Strategies that prevent initial HIV infection of cells are greatly needed. In this study, we determined the requirement of divalent cations for HIV infection of and attachment to peripheral blood mononuclear cells (PBMC), which contain several types of HIV-infectable cells-CD4(+) T cells, monocytes and dendritic cells. EDTA, added only during PBMC exposure to HIV, reduced infection by an average of 92%. The reduction of infection by EDTA was accompanied by a reduction in HIV binding to PBMC; R5, X4 and dual-tropic HIV binding to PBMC were inhibited by >85%. EGTA similarly reduced HIV binding to PBMC, while addition of Ca(2+) or Mn(2+), but not Mg(2+), fully restored binding. Virus attachment was inhibited in a dose-dependent manner by trypsin treatment of PBMC, indicating protein involvement in HIV binding. In contrast, mannan or soluble ICAM-1 did not inhibit HIV binding to PBMC. These data indicate that a Ca(2+)-dependent cell-surface protein(s) is responsible for the majority of HIV attachment to and infection of PBMC. Further studies of this are likely to reveal novel strategies to prevent infection of PBMC.
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