title: An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction.
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 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.
authors.affiliation: Animal Model Division and Divisions of Basic Science, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: W
authors.initials: W
authors.lastname: Reid
authors.forename: M
authors.initials: M
authors.lastname: Sadowska
authors.forename: F
authors.initials: F
authors.lastname: Denaro
authors.forename: S
authors.initials: S
authors.lastname: Rao
authors.forename: J
authors.initials: J
authors.lastname: Foulke
authors.forename: N
authors.initials: N
authors.lastname: Hayes
authors.forename: O
authors.initials: O
authors.lastname: Jones
authors.forename: D
authors.initials: D
authors.lastname: Doodnauth
authors.forename: H
authors.initials: H
authors.lastname: Davis
authors.forename: A
authors.initials: A
authors.lastname: Sill
authors.forename: P
authors.initials: P
authors.lastname: O'Driscoll
authors.forename: D
authors.initials: D
authors.lastname: Huso
authors.forename: T
authors.initials: T
authors.lastname: Fouts
authors.forename: G
authors.initials: G
authors.lastname: Lewis
authors.forename: M
authors.initials: M
authors.lastname: Hill
authors.forename: R
authors.initials: R
authors.lastname: Kamin-Lewis
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.forename: P
authors.initials: P
authors.lastname: Ray
authors.forename: R C
authors.initials: RC
authors.lastname: Gallo
authors.forename: M
authors.initials: M
authors.lastname: Reitz
authors.forename: J
authors.initials: J
authors.lastname: Bryant
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017353:Gene Deletion; D015750:Genes, gag; D015751:Genes, pol; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics*; D051381:Rats; D019076:Transgenes