Macrophages transmit human immunodeficiency virus type 1 products to CD4-negative cells: involvement of matrix

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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

Claudia Muratori1, Antonella Sistigu, Eliana Ruggiero

  • 1Division of Pathogenesis of Retroviruses, National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.

Journal of Virology
|June 22, 2007
PubMed

Insights

Human immunodeficiency virus type 1 (HIV-1) can spread from infected macrophages to CD4-negative cells via cell-to-cell contact. This transmission of HIV-1 products occurs without viral release and may contribute to AIDS pathogenesis.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4 lymphocytes.
  • Previous understanding suggested HIV-1 spreads mainly through cell-to-cell transmission within CD4 lymphocytes.

Purpose of the Study:

  • To investigate alternative mechanisms of HIV-1 transmission.
  • To determine if HIV-1-infected cells other than lymphocytes can transmit viral products.
  • To explore the role of macrophages in HIV-1 spread to non-lymphoid cells.

Main Methods:

  • Co-cultivation of HIV-1-infected macrophages with CD4-negative epithelial, neuronal, and endothelial cells.
  • Microscopic analysis to detect transfer of HIV-1 products.
  • Assessment of dependence on cell-to-cell contact and viral particle release.
  • Investigation of the role of specific HIV-1 proteins (Env, Nef) and matrix metalloproteinase 9 (MMP-9).

Main Results:

  • HIV-1-infected macrophages, but not lymphocytes, transmit HIV-1 products to diverse CD4-negative cells.
  • Transmission occurs rapidly (within 1 hour) and requires cell-to-cell contact, independent of viral particle release.
  • HIV-1 product transfer involves polarization and colocalization at virological synapses.
  • Increased matrix metalloproteinase 9 production by donor cells significantly contributes to this transmission.

Conclusions:

  • Macrophages can transfer HIV-1 products to CD4-negative cells through a contact-dependent mechanism.
  • This macrophage-driven transmission pathway, distinct from traditional viral spread, may play a crucial role in the pathogenesis of Acquired Immunodeficiency Syndrome (AIDS).
  • The involvement of MMP-9 highlights a potential therapeutic target for limiting HIV-1 spread.

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