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Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
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Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1

Published on: September 5, 2016

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The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking

Audrey Dumas1, Gabrielle Lê-Bury1, Florence Marie-Anaïs1

  • 1Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France Centre National de la Recherche Scientifique UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.

The Journal of Cell Biology
|October 28, 2015
PubMed

Insights

Human immunodeficiency virus type 1 (HIV-1) impairs macrophage bacterial clearance by disrupting phagosome maturation. The viral protein Vpr interferes with microtubule dynamics, hindering phagolysosome biogenesis in infected cells.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) infection impairs macrophage functions, but the underlying molecular mechanisms are not fully understood.
  • Macrophages play a critical role in host defense, including phagocytosis and bacterial clearance.

Purpose of the Study:

  • To investigate the molecular basis of impaired macrophage function in HIV-1 infection.
  • To elucidate the role of HIV-1 viral proteins in disrupting phagosome maturation and function.

Main Methods:

  • Analysis of phagosome maturation markers (late endocytic markers, hydrolases, reactive oxygen species) in HIV-1-infected macrophages.
  • Investigation of the endosomal sorting machinery, specifically EHD3/MICAL-L1.
  • Examination of the interaction between HIV-1 viral protein Vpr and host cell proteins (EB1, p150(Glued), dynein heavy chain).
  • Assessment of microtubule dynamics and phagosome trafficking.

Main Results:

  • HIV-1-infected macrophages exhibited impaired responses to phagocytic triggers and reduced bacterial clearance.
  • Phagosome maturation was perturbed in infected macrophages, arresting at the EHD3/MICAL-L1 endosomal sorting stage.
  • The viral regulatory protein Vpr was identified as crucial for disrupting phagosome maturation.
  • Vpr interacted with EB1, p150(Glued), and dynein, altering microtubule plus end localization and centripetal phagosome movement.

Conclusions:

  • HIV-1 infection, particularly through the Vpr protein, disrupts microtubule-dependent endocytic trafficking in macrophages.
  • This disruption leads to impaired phagolysosome biogenesis and contributes to the functional defects of macrophages in HIV-1-infected individuals.
  • Vpr acts as a key modulator of microtubule dynamics, affecting essential macrophage functions.

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