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

  • W. Reid
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • M. Sadowska
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • F. Denaro
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • S. Rao
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • J. Foulke
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • N. Hayes
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • O. Jones
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • D. Doodnauth
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • H. Davis
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • A. Sill
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • P. O'Driscoll
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • D. Huso
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • T. Fouts
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • G. Lewis
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • M. Hill
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • R. Kamin-Lewis
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • C. Wei
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • P. Ray
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • R. C. Gallo
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • M. Reitz
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...
  • J. Bryant
    Animal Model Division and Divisions of Basic Science, Vaccine Research, and Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Division of Comparative Medicine and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201; Division of Thoracic and Cardiovascular Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201; Children's Research Institute, Children's National Medical Center, Washington, DC...

抄録

<jats:p> 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 <jats:italic>gag</jats:italic> and <jats:italic>pol</jats:italic> , 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 cells 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 resulting 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. </jats:p>

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