Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy

Nat Med. 2002 May;8(5):522-6. doi: 10.1038/nm0502-522.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Biopsy
  • DNA Primers
  • Gene Products, env / genetics
  • HIV Infections / complications*
  • HIV Infections / pathology
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Kidney / pathology
  • Kidney / virology*
  • Kidney Diseases / pathology
  • Kidney Diseases / virology*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Urothelium / pathology
  • Urothelium / virology*
  • Virus Replication*


  • DNA Primers
  • Gene Products, env

Associated data

  • GENBANK/AF401048
  • GENBANK/AF401050
  • GENBANK/AF401051
  • GENBANK/AF401053
  • GENBANK/AF401054
  • GENBANK/AF401055
  • GENBANK/AF401325
  • GENBANK/AF401326
  • GENBANK/AF401327
  • GENBANK/AF401328
  • GENBANK/AF401329
  • GENBANK/AF401330
  • GENBANK/AF401331
  • GENBANK/AF401335
  • GENBANK/AF401336
  • GENBANK/AF401337
  • GENBANK/AF401338
  • GENBANK/AF482965
  • GENBANK/AF482966
  • GENBANK/AF482967
  • GENBANK/AF482968
  • GENBANK/AF482969
  • GENBANK/AF482970
  • GENBANK/AF482971
  • GENBANK/AF482972
  • GENBANK/AF482973
  • GENBANK/AF482974
  • GENBANK/AF482975
  • GENBANK/AF482976
  • GENBANK/AF482977
  • GENBANK/AF482978
  • GENBANK/AF482979