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Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
07:32

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

Published on: September 5, 2016

Human macrophages accumulate HIV-1 particles in MHC II compartments

Graça Raposo1, Marilyn Moore, Donald Innes

  • 1Institut Curie, CNRS UMR 144, Paris, France. graposo@curie.fr

Traffic (Copenhagen, Denmark)
|September 17, 2002
PubMed

Insights

Human macrophages infected with HIV-1 accumulate virus particles in specialized compartments. These compartments, rich in MHC class II and CD63, suggest a novel site for viral assembly and release.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Macrophages are key targets for Human Immunodeficiency Virus type 1 (HIV-1) infection.
  • The intracellular location where HIV-1 virions are harbored within macrophages remains unidentified.
  • Understanding HIV-1's intracellular trafficking is crucial for developing effective antiviral strategies.

Purpose of the Study:

  • To identify the specific intracellular organelle where HIV-1 accumulates in primary human macrophages.
  • To elucidate the mechanism of HIV-1 assembly and release within these cells.

Main Methods:

  • Extensive immuno-electron microscopy analysis of primary human macrophages infected in vitro with HIV-1.
  • Labeling of virus particles and cellular compartments for specific viral proteins (p24, gp120) and host cell markers (MHC class II, CD63, Lamp 1).

Main Results:

  • HIV-1 particles were consistently found within intracellular multivesicular compartments.
  • These compartments were enriched in major histocompatibility complex class II (MHC class II) molecules and CD63.
  • Virus particles showed strong labeling for HIV-1 p24 antigen, MHC class II, and CD63, suggesting these proteins are incorporated during assembly.
  • Evidence suggests viral assembly and budding occur within these MHC class II compartments, similar to multivesicular body formation.
  • Direct fusion of the virus-containing compartment with the plasma membrane was observed, leading to massive viral release.

Conclusions:

  • HIV-1 utilizes major histocompatibility complex class II compartments (MHC class II compartments) for viral assembly and replication in macrophages.
  • Viral budding within these compartments leads to the acquisition of host-derived proteins like MHC class II and CD63.
  • This process explains the unique lipid and protein composition of the viral envelope.
  • The study reveals a novel mechanism for HIV-1 release from infected macrophages via fusion of MHC class II compartments with the cell surface.

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