动物造模,药效评价,HIV感染 z-bio 2024-09-25 455

　　(1) The replication method involves using plasma or virus culture supernatant from AIDS patients (HIV-1), or peripheral blood mononuclear cells (PBMCs) from animals infected with HIV in vitro, or whole blood or free virus from infected animals; Adult chimpanzees were infected by intravenous injection, with a viral dose of 1000000TCID50/ml. Neutralizing antibodies can be detected in chimpanzee serum 10-12 weeks after vaccination, and the antibodies can be maintained for 48 weeks without opportunistic infections; At the same time, there was a temporary inversion in the ratio of CD4+T cells to CD8+T cells. Regardless of the infection route, the virus can be detected in peripheral blood mononuclear cells of model animals. In the fourth week of infection, HIV-1 specific antibodies (IgG, IgM) can be detected in chimpanzee serum using enzyme immunoassay (EIA), immunoblotting, and radioimmunoprecipitation (RIP).

　　(2) After being infected with HIV, the lymphoid tissue of chimpanzees is the main site of HIV replication and the main site of HIV specific lesions that lead to immune deficiency in the body. Viruses can cause chronic activation of the body's immune system, leading to loss of CD4+T cells and loss of function. Model animals can still develop lymphadenitis and bloodstream infections, and can produce immune responses to live viruses, with HIV-1 specific antibodies appearing in the blood. This model is widely used in anti-HIV-1 drug trials and pathological research, especially in the study of its non pathogenic mechanism and for vaccine development. However, chimpanzees are dangerous animals with limited sources, high prices, and non operability, which limits the application value of this model. (3) The early symptoms of HIV-1 infection in chimpanzees are very similar to those in human patients, such as lymph node enlargement, fever, weight loss, diarrhea, etc., but the late stage manifestations of the two infections are not the same; Chimpanzees do not show any clinical symptoms in the late stage of HIV infection, indicating a high sensitivity to HIV-1 and can be used as an acute HIV-1 infection model. Baboons and monkeys infected with HIV can also show lymphadenitis, but it cannot develop into the pathomorphological process of AIDS. Due to the genetic characteristics of chimpanzees (especially the histocompatibility complex) being closer to humans than baboons and monkeys, shortly after the isolation of human immunodeficiency virus 1 (HW-1) from AIDS patients, chimpanzees were used as model animals to inoculate HIV-1 infected human monocytes, which resulted in bloodstream infections but did not exhibit clinical manifestations and disease characteristics similar to those of clinical AIDS patients. In recent years, research reports have shown that chimpanzees infected with HIV-1 only develop clinical manifestations and disease characteristics similar to AIDS after several years. Therefore, this model has important value in the study of limiting virus replication mechanisms.