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Human immunodeficiency virus (HIV)-1 has been demonstrated to contribute to the pathogenesis of HIV-associated nephropathy. In renal biopsy studies, podocytes have been reported to be infected by HIV-1. However, the mechanism involved in HIV-1 internalization into podocytes is not clear. In the present study, we evaluated the occurrence of HIV-1 internalization into conditionally immortalized human podocytes and the mechanism involved. Human podocytes rapidly internalized R5 and X4 HIV-1 primary strains via an endocytosis-dependent pathway, without establishing a productive infection. The HIV-1 internalization was dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) receptor mediated. The role of DC-SIGN was confirmed by using specific blocking antibodies and transfection with small interfering (si) RNA/DC-SIGN. Since podocyte HIV-1 trafficking was not altered by pH-modulating agents, it appeared that HIV-1 routing occurred through nonacid vesicular compartments. Interestingly, transfection of podocytes with neither siRNA/caveolin-1 nor siRNA/clathrin heavy chain inhibited podocyte viral accumulation. Thus it appears that clathrin-coated vesicles and caveosomes may not be contributing to HIV-1-associated membrane traffic.
|Translated title of the contribution||DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes|
|Pages (from-to)||F664 - F673|
|Number of pages||10|
|Journal||AJP - Renal Physiology|
|Publication status||Published - Sep 2010|
Mikulak, J., Teichberg, S., Arora, S., kumar, D., Kumar, D., Yadav, A., Salhan, D., Pullagura, S., Mathieson, PW., Saleem, MA., & Singhal, P. (2010). DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes. AJP - Renal Physiology, 299(3), F664 - F673. https://doi.org/10.1152/ajprenal.00629.2009