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Macrophage bridging conduit trafficking of HIV-1 through the endoplasmic reticulum and Golgi network

Irena Kadiu1, Howard E Gendelman

  • 1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5800, USA.

Journal of Proteome Research
|May 14, 2011
PubMed

Insights

Human immunodeficiency virus type I (HIV-1) uses bridging conduits to spread between cells. This study reveals how HIV-1 hijacks endosomes and the ER-Golgi network within these conduits for efficient intercellular transfer.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Bridging conduits (BC) are cellular structures enabling material exchange between connected cells.
  • The human immunodeficiency virus type I (HIV-1) is known to spread between cells, but the mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms by which HIV-1 utilizes bridging conduits for intercellular spread.
  • To investigate the role of endosomes, endoplasmic reticulum (ER), and Golgi apparatus in HIV-1 transfer through BC.

Main Methods:

  • Proteomic, biochemical, and advanced imaging techniques were employed.
  • Analysis of isolated bridging conduits from human monocyte-derived macrophages.
  • Tracking of viral proteins and fluorescently labeled HIV-1 within cellular organelles.

Main Results:

  • HIV-1 proteins and cellular markers for endosomes, ER, and Golgi were identified within BC.
  • The ER and Golgi exhibited tubular extensions into BC in polarized macrophages.
  • HIV-1 components were found sequestered in endocytic and ER-Golgi organelles, utilizing retrograde transport for trafficking.
  • Disruption of the ER-Golgi network impeded HIV-1 transport within BC endosomes.

Conclusions:

  • HIV-1 exploits bridging conduits to enhance its spread and evade immune detection.
  • Intercellular HIV-1 transfer is mediated by endosome transport through BC.
  • The ER and Golgi apparatus play a critical role in directing HIV-1 cell-to-cell transfer via bridging conduits.

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