Kopp JB, Weeks BS, Marinos NJ, Bryant JL, Dickie P, Notkins AL, Klotman PE; International Conference on AIDS.
Int Conf AIDS. 1991 Jun 16-21; 7: 64 (abstract no. TU.B.31).
Laboratory of Developmental Biology, NIH, Bethesda, MD, USA
OBJECTIVE: The objective of these studies was to investigate the role of viral gene products in the pathogenesis of HIV-associated nephropathy (HIVAN). METHODS: We established a transgenic mouse model using a non-infectious HIV-1 provirus with a 3 kb deletion overlapping gag and pol genes. This construct contained the LTRs and encoded envelope and the regulatory proteins Tat, Rev, Nef, Vif, Vpr, & Vpu. RESULTS: Southern blots of 2 lines indicated that multiple proviral copies were integrated into different and unique sites. Heterozygous mice developed proteinuria by age 25 and died of azotemia between 60 and 100 days. Light microscopy showed focal segmental glomerulosclerosis, microcystic tubular dilatation, and a sparse monocytic interstitial infiltrate. Indirect immunofluorescence revealed increased glomerular deposition of laminin, collagen IV, fibronectin, and heparan sulfate proteoglycan. Northern analysis of total kidney RNA demonstrated doubly-spliced, singly-spliced, and unspliced proviral transcripts. Kidney immunoblots demonstrated polypeptides corresponding to GP41. Indirect immunofluorescent analysis showed Rev protein in sclerotic glomeruli. CONCLUSIONS: In this transgenic model, HIV-1 genes are expressed in the kidney and expression is associated with renal pathology closely resembling that of AIDS patients. These findings implicate HIV-1 proteins in the pathogenesis of HIVAN.
Publication Types:
Keywords:
- AIDS Vaccines
- AIDS-Associated Nephropathy
- Acquired Immunodeficiency Syndrome
- Animals
- Gene Products, rev
- Gene Products, tat
- Genes, tat
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Kidney
- Kidney Glomerulus
- Mice
- Mice, Transgenic
- Proviruses
- genetics
Other ID:
UI: 102184223
From Meeting Abstracts