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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
Abstract:
Macrophages are important targets for HIV-1 infection and harbor the virions in an as yet unidentified organelle. To determine the location of HIV-1 in these cells, an extensive analysis of primary human macrophages infected in vitro with HIV-1 was carried out by immuno-electron microscopy. Virus particles were found to accumulate in intracellular multivesicular compartments which were enriched in major histocompatibility complex class II molecules and CD63. These features are characteristics of major histocompatibility complex class II compartments where maturing class II molecules acquire their peptide cargo. The membrane-delimited, electron-dense virus particles of 100-110 nm diameter labeled strongly for HIV-1 p24 antigen, major histocompatibility complex class II molecules, CD63 and, to a lesser extent for HIV-1 gp120 envelope protein and Lamp 1. Our data suggest that virus particles may access the lumen of the major histocompatibility complex class II compartment by budding from the limiting membrane, thus acquiring proteins of this membrane such as class II and CD63. Viral assembly and budding would therefore occur in macrophages by a process similar to the formation of the internal vesicles in multivesicular bodies and at the same location. This could account for the particular content in lipids and proteins previously found in the membrane wrapping HIV particles. Our observations also suggest direct fusion of the virus containing major histocompatibility complex class II compartment with the plasma membrane, leading to massive release of viral particles into the extracellular medium.
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.