DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes

J. Mikulak, S. Teichberg, S. Arora, D. Kumar, A. Yadav, D. Salhan, S. Pullagura, P. W. Mathieson, M. A. Saleem, P. C. Singhal

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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. DC-SIGN; DEC 205; HIV-1 receptor; HIV-associated nephropathy

Original languageEnglish (US)
Pages (from-to)F664-F673
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number3
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Mikulak, J., Teichberg, S., Arora, S., Kumar, D., Yadav, A., Salhan, D., Pullagura, S., Mathieson, P. W., Saleem, M. A., & Singhal, P. C. (2010). DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes. American Journal of Physiology - Renal Physiology, 299(3), F664-F673. https://doi.org/10.1152/ajprenal.00629.2009