title: DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes.
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.
authors.affiliation: Departments of Medicine and Pathology, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mikulak
authors.forename: S
authors.initials: S
authors.lastname: Teichberg
authors.forename: S
authors.initials: S
authors.lastname: Arora
authors.forename: D
authors.initials: D
authors.lastname: Kumar
authors.forename: A
authors.initials: A
authors.lastname: Yadav
authors.forename: D
authors.initials: D
authors.lastname: Salhan
authors.forename: S
authors.initials: S
authors.lastname: Pullagura
authors.forename: P W
authors.initials: PW
authors.lastname: Mathieson
authors.forename: M A
authors.initials: MA
authors.lastname: Saleem
authors.forename: P C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D051242:Caveolin 1 / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D002966:Clathrin / Q000235:genetics; D004705:Endocytosis / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000502:physiology*; D050199:Podocytes / Q000166:cytology / Q000821:virology*; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology*; D014162:Transfection; D053586:Virus Internalization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D002966:Clathrin; D037181:Lectins, C-Type; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C495540:CAV1 protein, human