HIV Type 1 Nef is released from infected cells in CD45(+) microvesicles and is present in the plasma of HIV-infected

A D Raymond1, T C Campbell-Sims, M Khan

  • 1Morehouse School of Medicine, Atlanta, Georgia 30310, USA.

Insights

Human immunodeficiency virus type 1 Nef protein is released from infected cells within microvesicles. This microvesicular Nef (mvNef) is found in patient plasma and induces T-cell apoptosis, potentially contributing to AIDS pathogenesis.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) Nef protein is crucial for viral persistence, infectivity, and AIDS progression.
  • Nef is detected in plasma and released from infected cells, but its release form was unknown.
  • Nef is a myristoylated protein interacting with intracellular vesicular trafficking.

Purpose of the Study:

  • To determine the form in which HIV-1 Nef is released from infected cells.
  • To investigate the presence and characteristics of extracellular Nef in HIV-infected individuals.
  • To assess the biological activity of extracellular Nef on immune cells.

Main Methods:

  • Detection and quantification of Nef in microvesicles from infected cell cultures and patient plasma.
  • Analysis of microvesicular Nef (mvNef) levels in relation to viral load and CD4 count.
  • Assessment of the effect of mvNef on Jurkat T-lymphocytes and U937 monocytic cells.

Main Results:

  • HIV-1 Nef is released within CD45-containing microvesicles (mvNef).
  • mvNef is present at high concentrations (10 ng/ml) in the plasma of HIV-infected individuals.
  • Plasma mvNef levels did not correlate with viral load or CD4 count and persisted despite antiretroviral therapy.
  • Nef microvesicles induced apoptosis in Jurkat T-lymphocytes but not U937 cells.

Conclusions:

  • HIV-1 Nef is released extracellularly in microvesicles (mvNef).
  • mvNef is abundant in HIV-infected individuals' plasma and resistant to antiretroviral therapy.
  • mvNef's ability to induce T-cell apoptosis suggests a significant role in AIDS pathogenesis.

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