An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction

• DOI: 10.1073/pnas.161290298
• Publication Date: 2002-07-26T14:34:10Z
• Authors: W. Reid; M. Sadowska; F. Denaro; S. Rao; J. Foulke; N. Hayes; O. Jones; D. Doodnauth; H. Davis; A. Sill; P. O'Driscoll; D. Huso; T. Fouts; G. Lewis; M. Hill; R. Kamin-Lewis; C. Wei; P. Ray; R. C. Gallo; M. Reitz; J. Bryant
• Keywords: Keyhole limpet hemocyanin

We report, to our knowledge, the first HIV type 1 (HIV-1) transgenic (Tg) rat. Expression of transgene, consisting an HIV-1 provirus with a functional deletion gag and pol , is regulated by viral long terminal repeat. Spliced unspliced transcripts were expressed in lymph nodes, thymus, liver, kidney, spleen, suggesting that Tat Rev are functional. Viral proteins identified spleen tissue sections immunohistochemistry gp120 was present splenic macrophages, T B cells, serum. Clinical signs included wasting, mild severe skin lesions, opaque cataracts, neurological signs, respiratory difficulty. Histopathology selective loss splenocytes within periarterial lymphoid sheath, increased apoptosis endothelial cells splenocytes, follicular hyperplasia lymphocyte depletion mesenteric interstitial pneumonia, psoriatic neurological, cardiac, renal pathologies. Immunologically, delayed-type hypersensitivity response keyhole limpet hemocyanin diminished. By contrast, Ab titers proliferative recall antigen (keyhole hemocyanin) normal. The Tg rat thus has many similarities humans infected expression genes, immune-response alterations, pathologies resulting from infection. may provide valuable model for some pathogenic manifestations chronic diseases could be useful testing therapeutic regimens targeted stages replication subsequent proviral integration.