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1.
J Infect Dis ; 175(6): 1337-43, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9180172

ABSTRACT

Pediatric AIDS typically follows transmission of human immunodeficiency virus type 1 (HIV-1) from infected mothers to their offspring. The possibility that infected maternal-origin cells serve as a conveyance for mother-to-child HIV-1 transmission was investigated in a rabbit infection model. Administration of HIV-1-infected human T cells to pregnant rabbits was followed by evaluation of offspring, from newborn to 1.5 years of age. HIV-1 was detected in 11 of 19 vaginally delivered offspring born to mothers given infected cells during gestation. Interstitial pneumonias or lymphoid organ lesions, similar to those seen in human pediatric AIDS, occurred in some offspring. Persistence of inoculum cell (HLA)-specific gene sequences in offspring indicated that vertical transmission can be effected by T cell-associated virus. These results along with features of rabbit biology, including primate-type placentation, short gestation, and delivery of litters, suggest that the rabbit model is advantageous for studies of perinatal HIV-1 transmission.


Subject(s)
HIV Infections/transmission , HIV-1 , Infectious Disease Transmission, Vertical , T-Lymphocytes/virology , Amino Acid Sequence , Animals , Animals, Newborn , Base Sequence , DNA, Viral/analysis , Female , Genes, MHC Class I/genetics , HIV Antibodies/blood , HIV-1/isolation & purification , HLA-C Antigens/blood , Humans , Molecular Sequence Data , Pregnancy , Rabbits , Spleen/virology , T-Lymphocytes/transplantation , Thymus Gland/virology , Viscera/pathology
2.
J Infect Dis ; 173(3): 722-6, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8627039

ABSTRACT

Skin diseases ranging from infective dermatitis to cutaneous lymphoma have been associated with human T cell leukemia virus (HTLV) type I. A generalized exfoliative papillated dermatopathy occurred in a rabbit 20 months into a course of chronic HTLV-I infection. Biopsies revealed epidermotropic T cell infiltrates, including Sezary-like cells, that resulted in a pattern mimicking cutaneous T cell lymphoma. HTLV-I was isolated from affected skin, and virus expression was detected in cutaneous cultures. Sezary-like cells also occurred in circulation. Interleukin-2-independent lymphocyte cultures, established from blood exhibiting elevated CD8 T cell levels and CD25 expression, had polyclonal integration of provirus. The findings are similar to those in evolving adult T cell leukemia lymphoma and may represent a prelymphomatous change. The cutaneous lymphoproliferative lesion resulted from HTLV-I infection and further establishes the New Zealand White rabbit inoculated with the RH/K34 cell line as a suitable model for investigation of HTLV-I pathogenesis.


Subject(s)
HTLV-I Infections/etiology , Skin Diseases, Viral/etiology , Adult , Animals , Base Sequence , Chronic Disease , DNA Probes/genetics , DNA, Viral/genetics , DNA, Viral/isolation & purification , Disease Models, Animal , Genes, env , HTLV-I Infections/pathology , HTLV-I Infections/virology , Human T-lymphotropic virus 1/genetics , Human T-lymphotropic virus 1/isolation & purification , Humans , Male , Molecular Sequence Data , Rabbits , Skin Diseases, Viral/pathology , Skin Diseases, Viral/virology
3.
Lab Invest ; 74(3): 696-710, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8600320

ABSTRACT

Human T cell leukemia virus type I (HTLV-1) infection may lead to an acutely fatal adult T cell leukemia-lymphoma (ATLL), but HTLV-1-infected people usually remain asymptomatic. Why only certain HTLV-I infections lead to acute ATLL, which is characterized by leukemic infiltration of multiple organs and immune suppression, remains unknown. A readily accessible animal model in which the spectrum of consequences resulting from HTLV-I infection can be observed would greatly aid studies of this retrovirus. New Zealand White rabbits inoculated with either HTLV-1-infected CD25+ T cells or cell-free virus, were serially necropsied at different intervals after death or humane sacrifice. Tissues were preserved at necropsy or cultured in vitro and subsequently prepared for morphologic or molecular examination. Rabbits inoculated with RH/K34, a productively infected rabbit T cell line that contains a monoclonally integrated full-length HTLV-I provirus, developed acute ATLL-like biologically malignant lymphoproliferative disease with lymphocyte infiltration of viscera; lymphomas consisting primarily of monoclonal expansions of RH/K34 manifested a variety of diffuse pleomorphic histologic types. Concurrently, lymphoproliferative disease was associated with onset of thymic atrophy in the presence of rapidly increasing thymic proviral load. In contrast, rabbits given two other HTLV-1 inocula, originally derived (as was RH/K34) using the human T cell line MT-2 as virus source, also became infected but did not develop thymic atrophy or the ATLL-like disease. HTLV-1 infection, thymic atrophy, and leukemic infiltration similar to acute ATLL occurred reproducibly in a New Zealand White rabbit model independent of RH/K34 inoculum and host histocompatibility. Thymic atrophy in RH/K34-inoculated rabbits, but not in rabbits given other similar HTLV-1, was consistent with immunosuppression sufficient to prevent rejection of the inoculum. Although the short, 8-day course of the experimental ATLL precludes its having a molecular pathogenesis identical to the human condition, the systemic consequences of acute ATLL, including its association with thymic atrophy, are closely modeled.


Subject(s)
HTLV-I Infections/complications , HTLV-I Infections/pathology , Leukemia-Lymphoma, Adult T-Cell/etiology , Leukemia-Lymphoma, Adult T-Cell/pathology , Thymus Gland/pathology , Adult , Animals , Disease Models, Animal , Female , HTLV-I Infections/immunology , Human T-lymphotropic virus 1/pathogenicity , Humans , Immunogenetics , Leukemia-Lymphoma, Adult T-Cell/immunology , Lung/pathology , Lymph Nodes/immunology , Lymph Nodes/pathology , Major Histocompatibility Complex , Rabbits , Spleen/immunology , Spleen/pathology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Thymus Gland/immunology
4.
AIDS Res Hum Retroviruses ; 11(2): 297-306, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7742043

ABSTRACT

Rabbits can be infected with human immunodeficiency virus (HIV-1), but no disease signs similar to acquired immunodeficiency syndrome (AIDS) have been reported to date. In our attempt to develop types of HIV-1 more virulent for rabbits, an immunodeficiency characterized by CD4+ lymphocytopenia and opportunistic infection was induced by transfusion from HIV-1-infected rabbits. The original donor was infected for 27 months; initial passage resulted in infection of two rabbits. Transfusions from these two infected rabbits. Transfusions from these two infected rabbits caused immunodeficiency in 12 recipients. One rabbit died at 3 months and a second at 8 months postransfusion with lymphocyte depletion in lymphoid organs; one of these and another of the CD4+ lymphocytopenic rabbits had opportunistic infections. Lentivirus-like particles were detected in thymus and spleen from an affected rabbit. Despite appearance of AIDS-like disease signs, antibodies to HIV-1 probes were detected in rabbits receiving passaged blood. However, RNA transcripts hybridizing with HIV-1 probes were detected in organs of some rabbits, implicating the initial HIV infection in the disease. Transfusion from uninfected donors produced no signs of immunodeficiency, which suggests the involvement of an HIV-related agent. The present data do not allow definitive characterization of the agent(s) involved in the immunodeficiency. Possibilities include activation of a rabbit retrovirus or, alternatively, development of a mutated HIV-1 strain.


Subject(s)
Blood/virology , CD4-Positive T-Lymphocytes/pathology , HIV Infections/transmission , HIV-1/pathogenicity , Immunologic Deficiency Syndromes/virology , Animals , Blood Transfusion , HIV Infections/immunology , HIV Infections/physiopathology , HIV-1/immunology , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/physiopathology , Lymph Nodes/virology , Microscopy, Electron , RNA, Viral/analysis , Rabbits , Spleen/ultrastructure , Spleen/virology , Thymus Gland/ultrastructure , Thymus Gland/virology
5.
J Am Vet Med Assoc ; 197(11): 1493-4, 1990 Dec 01.
Article in English | MEDLINE | ID: mdl-2272882

ABSTRACT

Prostatic adenocarcinoma was diagnosed in an 11-year-old neutered cat. Clinical signs of the disease included hematuria and a mass in the caudal portion of the abdomen. Prostatectomy was performed. Doxorubicin was administered IV at a dosage of 30 mg/m2 of body surface, followed by cyclophosphamide (300 mg/m2, IV). After 4 treatments, low urine specific gravity and proteinuria developed, and treatment was discontinued. The cat was euthanatized 10 months after surgery because of recurrence of the neoplasm. Necropsy revealed metastasis to the lungs and pancreas.


Subject(s)
Adenocarcinoma/veterinary , Cat Diseases/surgery , Neoplasm Recurrence, Local/veterinary , Prostatic Neoplasms/veterinary , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Animals , Cat Diseases/drug therapy , Cats , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Male , Prostatectomy/veterinary , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery
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