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DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes
J Mikulak1, S Teichberg, S Arora
1Departments of Medicine and Pathology, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, NY, USA.
American Journal of Physiology. Renal Physiology
|July 16, 2010
Summary
Human immunodeficiency virus (HIV)-1 enters human podocytes through endocytosis, mediated by the DC-SIGN receptor. This process does not lead to a productive infection, suggesting a novel pathway in HIV-associated nephropathy.
Area of Science:
- Nephrology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV)-1 contributes to HIV-associated nephropathy.
- Podocytes are implicated in HIV-1 pathogenesis and show evidence of viral infection.
- The mechanism of HIV-1 entry into podocytes remains unclear.
Purpose of the Study:
- To investigate the internalization of HIV-1 into human podocytes.
- To elucidate the mechanism and cellular receptors involved in HIV-1 uptake by podocytes.
Main Methods:
- Utilized conditionally immortalized human podocytes.
- Assessed HIV-1 internalization using primary R5 and X4 strains.
- Employed blocking antibodies and small interfering RNA (siRNA) targeting DC-SIGN, caveolin-1, and clathrin heavy chain.
- Investigated the role of pH-modulating agents in viral trafficking.
Main Results:
- Human podocytes rapidly internalized R5 and X4 HIV-1 strains via endocytosis.
- HIV-1 uptake was dependent on the dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) receptor.
- Blocking DC-SIGN or using siRNA/DC-SIGN significantly inhibited viral internalization.
- HIV-1 trafficking was not affected by pH-modulating agents, indicating nonacid vesicular compartments.
- Neither siRNA/caveolin-1 nor siRNA/clathrin heavy chain inhibited podocyte viral accumulation, suggesting these pathways are not involved.
Conclusions:
- HIV-1 enters human podocytes through a DC-SIGN-mediated endocytosis pathway.
- The internalization process does not result in a productive HIV-1 infection in podocytes.
- HIV-1 trafficking occurs via nonacid vesicular compartments, independent of clathrin-coated vesicles and caveosomes.
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