RESUMO
Serial virus specimens rescued from rabbits, experimentally infected with bovine immunodeficiency (BIV) strain R29, were monitored for changes in quasispecies population, using the single-strand conformation polymorphism (SSCP) analysis. The generation of characteristic SSCP patterns enables the rapid differentiation of BIV variants derived from the conserved part on the env region of the BIV genome, reducing the need for expensive and time-consuming direct sequencing analyses. Our results showed genetic polymorphism among a number of sampled BIV population in experimentally infected rabbits. At least three SSCP patterns (BIV quasispecies) were detected. The SSCP analysis allows for an easy, sensitive, and rapid screening of genetic variants of the virus and the assessment of variation at a number of tissue target sites. These variations may relate to cell-type targets and/or disease progression, and could be significant to our understanding of lentiviral pathogenesis.
Assuntos
Variação Genética , Vírus da Imunodeficiência Bovina/classificação , Vírus da Imunodeficiência Bovina/genética , Infecções por Lentivirus/virologia , Polimorfismo Conformacional de Fita Simples , Animais , Bovinos , Modelos Animais de Doenças , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Vírus da Imunodeficiência Bovina/isolamento & purificação , Vírus da Imunodeficiência Bovina/patogenicidade , Infecções por Lentivirus/fisiopatologia , Reação em Cadeia da Polimerase/métodos , CoelhosRESUMO
To assess the value of bovine immunodeficiency virus (BIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunologic functions in New Zealand white rabbits experimentally infected with an uncloned virulent isolate of the virus, BIV R29. Serum samples were tested by Western blot for the presence and persistence of antibody production. The T- and B-lymphocyte function was studied by evaluation of the blastogenic responsiveness to concanavalin A (Con A) and to dextran sulfate (DxS). All infected rabbits seroconverted to BIV antigens within 2 to 4 weeks postinfection (p.i.) The BIV was isolated from the peripheral blood lymphocytes (PBLs) of 13 of 17 rabbits (77%) early in the infection and also from 5 of 17 hyperplastic mesenteric lymph nodes (29%) and 10 of 17 spleens (59%) during the chronic stage of infection. Seven of 17 BIV-infected rabbits (41%) developed marked immunodepression 2 to 5 months p.i., and later, 5 exhibited a rapidly progressive disease with anorexia, weight loss, neurologic impairment, splenomegaly, and mesenteric lymphadenopathy. These data underline the value of the BIV model for studying HIV pathogenesis in vivo and the development of interventional strategies for AIDS.
Assuntos
Modelos Animais de Doenças , Infecções por HIV , Vírus da Imunodeficiência Bovina/patogenicidade , Infecções por Lentivirus , Doenças Linfáticas , Animais , Anticorpos Antivirais/sangue , Western Blotting , Bovinos , Infecções por HIV/imunologia , HIV-1 , Humanos , Tolerância Imunológica , Vírus da Imunodeficiência Bovina/isolamento & purificação , Infecções por Lentivirus/imunologia , Infecções por Lentivirus/patologia , Infecções por Lentivirus/virologia , Fígado/patologia , Doenças Linfáticas/imunologia , Doenças Linfáticas/patologia , Doenças Linfáticas/virologia , Ativação Linfocitária , Coelhos , Baço/patologia , VirulênciaRESUMO
To investigate the effect of bovine immunodeficiency virus (BIV) infection on the rabbit immune system, we studied the proliferative responses of peripheral blood lymphocytes (PBLs) of rabbits experimentally inoculated with BIV. All BIV127-inoculated rabbits seroconverted after 6 weeks and remained seropositive over a prolonged period of time. Assays for specific lymphocyte reactivity to concanavalin A (Con A) were performed monthly for over 1 year. One-hundred percent of infected rabbits developed abnormally low T cell responses, as measured by Con A stimulation. By 3 months postinoculation, the PBL response to Con A was diminished and remained depressed for 6 months. All animals were clinically asymptomatic within 14 months of BIV inoculation. By 15 and 16 months postinoculation, two of three infected rabbits exhibited recurrent lowering of the T cell responsiveness including a decrease in absolute PBL counts. One of these animals died unexpectedly. Our results further confirmed that a functional impairment of lymphocytes was induced early in the course of BIV infection, prior to clinical disease. These findings suggested that BIV infection may mimic asymptomatic infection of human immunodeficiency virus (HIV) and provided further evidence of the importance of BIV-induced disease in rabbits as a relevant model for the study of AIDS.