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

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. ReitzJ. Bryant

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Abstract

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

Original languageEnglish (US)
Pages (from-to)9271-9276
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number16
DOIs
StatePublished - Jul 31 2001

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    Reid, W., Sadowska, M., Denaro, F., Rao, S., Foulke, J., Hayes, N., Jones, O., Doodnauth, D., Davis, H., Sill, A., O'Driscoll, P., Huso, D., Fouts, T., Lewis, G., Hill, M., Kamin-Lewis, R., Wei, C., Ray, P., Gallo, R. C., ... Bryant, J. (2001). An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 98(16), 9271-9276. https://doi.org/10.1073/pnas.161290298