Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy.
HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy. 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.
Marras
Daniele
D
Division of Nephrology, Department of Medicien, Mount Sinai School of Medicine, New York, New York, USA. daniele.marras@mssm.edu
Bruggeman
Leslie A
LA
Gao
Feng
F
Tanji
Nozomu
N
Mansukhani
Mahesh M
MM
Cara
Andrea
A
Ross
Michael D
MD
Gusella
G Luca
GL
Benson
Gary
G
D'Agati
Vivette D
VD
Hahn
Beatrice H
BH
Klotman
Mary E
ME
Klotman
Paul E
PE
D001483:Base Sequence; D001706:Biopsy; D017931:DNA Primers; D015686:Gene Products, env / Q000235:genetics; D015658:HIV Infections / Q000150:complications* / Q000473:pathology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000821:virology*; D007674:Kidney Diseases / Q000473:pathology / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D019459:Urothelium / Q000473:pathology / Q000821:virology*; D014779:Virus Replication
D017931:DNA Primers; D015686:Gene Products, env