Nature Medicine
8, 522 - 526 (2002)
doi:10.1038/nm0502-522
Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathyDaniele Marras1, Leslie A. Bruggeman1, Feng Gao6, Nozomu Tanji4, Mahesh M. Mansukhani4, Andrea Cara7, Michael D. Ross1, G Luca Gusella1, Gary Benson3, Vivette D. D'Agati4, Beatrice H. Hahn5, Mary E. Klotman2
& Paul E. Klotman11
Divisions of Nephrology, Mount Sinai School of Medicine, New York, New York, USA
2
Divisions of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
3
Department of Biomathematical Sciences, Mount Sinai School of Medicine, New York, New York, USA
4
Department of Pathology, Columbia Presbyterian Medical Center, New York, New York, USA
5
Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
6
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
7
Istituto Superiore di Sanita, Rome, Italy
Correspondence should be addressed to Daniele Marras daniele.marras@mssm.eduHIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease1,
2,
3,
4. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy5,
6,
7,
8. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy9. Here, to investigate whether renal epithelial cells were productively infected by HIV-1, we examined renal tissue for the presence of HIV-1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells were removed by laser-capture microdissection from biopsies of two patients, DNA was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from individually dissected cells by nested PCR. Phylogenetic analysis of kidney-derived sequences as well as corresponding sequences from peripheral blood mononuclear cells of the same patients revealed evidence of tissue-specific viral evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney-derived sequences formed tissue-specific subclusters within the radiation of blood mononuclear cell-derived viral sequences from both patients. These data, along with the detection of HIV-1-specific proviral DNA and mRNA in tubular epithelium cells, argue strongly for localized replication of HIV-1 in the kidney and the existence of a renal viral reservoir.
|
