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Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages

Sayaka Sukegawa1, Eri Miyagi1, Fadila Bouamr1

  • 1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Building 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, USA.

Cell Reports
|January 19, 2018
PubMed

Insights

Human mannose receptor 1 (hMRC1) acts as an antiviral factor, inhibiting HIV-1 release by clustering virions at the cell surface. HIV-1 evades this by downregulating hMRC1 expression in macrophages.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human mannose receptor 1 (hMRC1) is present on macrophages and dendritic cells.
  • hMRC1 facilitates HIV-1 binding and uptake by macrophages.
  • HIV-1 infection involves complex interactions between viral proteins and host cell receptors.

Purpose of the Study:

  • To investigate the role of hMRC1 in HIV-1 replication.
  • To identify hMRC1 as a potential antiviral factor.
  • To elucidate the mechanism by which hMRC1 affects HIV-1 release.

Main Methods:

  • Expression analysis of hMRC1 in immune cells.
  • HIV-1 infection assays in monocyte-derived macrophages (MDMs).
  • Analysis of virion release and infectivity in the presence of hMRC1.
  • Investigating the interaction between HIV-1 Env protein and hMRC1.

Main Results:

  • hMRC1 inhibits HIV-1 release via a BST-2-like mechanism, causing virion clustering at the cell surface.
  • Despite clustering, virions remained infectious.
  • HIV-1 actively counteracts hMRC1's antiviral effect through transcriptional silencing.
  • hMRC1's antiviral activity is independent of the HIV-1 Env protein, suggesting other cellular factors are involved.

Conclusions:

  • hMRC1 functions as an intrinsic antiviral factor in primary human macrophages.
  • HIV-1 employs downregulation of hMRC1 to overcome this host defense mechanism.
  • The findings reveal a novel antiviral pathway and viral evasion strategy in HIV-1 infection.
Keywords:
HIV-1mannose receptorrestriction factorvirus release

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