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Related Experiment Videos

HIV-1 preferentially binds receptors copatched with cell-surface elastase.

Cynthia L Bristow1, Danielle R Mercatante, Ryszard Kole

  • 1Laboratory of Cellular Physiology and Immunology, The Rockefeller University and Population Council, New York, NY 10021, USA. bristoc@mail.rockefeller.edu

Blood
|August 23, 2003
PubMed
Summary

Human leukocyte elastase (HLE) acts as an HIV-1 coreceptor, facilitating viral entry. Alpha-1 proteinase inhibitor (alpha1PI) functions as a cofactor, influencing HIV infectivity and disease progression.

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Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Human leukocyte elastase (HLE) is implicated in HIV-1 infection.
  • HLE's role in HIV-1 pathogenesis is not fully understood.
  • HLE localization varies between HIV-permissive and non-permissive cells.

Purpose of the Study:

  • To investigate the nonenzymatic receptor function of HLE in HIV-1 infection.
  • To determine the role of HLE and its ligand alpha1PI in HIV-1 binding and infectivity.
  • To explore the potential of HLE and alpha1PI as therapeutic targets for HIV-1 disease progression.

Main Methods:

  • Assessing HLE localization in HIV-permissive and non-permissive cells.
  • Manipulating HLE expression in HLE-null cells to evaluate HIV infectivity.

Related Experiment Videos

  • Quantifying HIV binding and infectivity in response to HLE RNA subtraction and alpha1PI concentration.
  • Analyzing the co-localization of HLE with canonical HIV receptors under different conditions.

    • Main Results:

    • HLE is localized to the cell surface in HIV-permissive cells and to granules in non-permissive cells.
    • Inducing cell-surface HLE expression on HLE-null cells restored HIV infectivity.
    • HIV binding and infectivity decreased with HLE RNA subtraction and showed dose dependence on alpha1PI.
    • Alpha1PI promoted, while chemokines prevented, the co-patching of HLE with canonical HIV receptors.

    Conclusions:

    • HLE functions as a nonenzymatic coreceptor for HIV-1.
    • Alpha-1 proteinase inhibitor (alpha1PI) acts as a cofactor, promoting HIV infectivity.
    • HLE and alpha1PI may play significant roles in HIV-1 pathogenesis and disease progression.