HIV病毒,动物模型 z-bo 2020-08-12 498

　　(1) Copy method

　　① The long terminal repeat (LTR) of HW-1 is linked to the indicator gene in transgenic mice, that is, the LTTR gene is linked to the indicator gene-chlorin acetyltransferase (CAT) and then introduced into mouse cells.

　　②HW-1 tat transgenic mice, that is, the tat gene sequence of ARV-2 (AIDS- associated retrovirus strain 2) virus is connected to the LTR of HIV-1 and introduced into the PML plasmid. The tat sequence is 179 bases, encoding the first Amino acids 8-66. The fragment was then injected into the fertilized egg cells of CD-1 male mice and C57BL/6×DBA male mice. The newborn mice were detected by Southern blot, and some mice expressed the sequence on the skin.

　　③ HIV full-sequence proviral DNA transgenic mice, that is, the transgenic DNA transgenic mice established after the establishment of the HIV-1 full-sequence prodrome and the T and t antigen genes of SV40 are complete, full-viral gene mice.

　　(2) Model features

　　① The expression of tissue-specific CAT was detected in the eyes, heart, thymus, and tail of the transgenic mice by linking the HIV-1 long terminal repeat (LTR) with the indicator gene. Peripheral blood lymphocytes and monocytes can also express CAT activity when pHA or cytokine is co-cultured, and CAT activity is the highest in skin Langerhans cells. Immunocytochemical staining technique was used to detect the LTR transcriptional activity of HIV-1 in the cerebral cortex, basal ganglia and cerebellar glial cells or small nerve cells. Although this transgenic mouse expresses the HIV-1 LTR gene in multiple organs and tissues, it only expresses it and does not cause the mice to develop corresponding diseases.

　　②The skin lesions of male mice of HIV-1 tat transgenic mice showed the proliferation and development of spindle cells, but the female mice had skin lesions or tumors, and at the same time there was a high incidence of liver cancer. At this time, the occurrence and development of tumors are indirectly affected by growth factors released from the skin mediated by tat genes. Also found. In this transgenic mouse model, a considerable part of animals have developed human-like Kaposi (Kaposi) sarcoma growth on the skin, which may be caused by HIV-1, especially tat gene products.

　　③For HIV full-sequence proviral DNA transgenic mice, although the complete full viral gene copy has been confirmed to be expressed in mice, the gene expression and disease signs cannot be found in all mice. The F1 offspring produced by sexual reproduction of a female mouse and a normal male mouse expressing the full sequence gene grow very slowly, with lymphocyte infiltration around blood vessels in the lungs, and epidermis on the tail, ears, nose, feet, etc. Hyperplasia, as well as lymphadenopathy and thymic atrophy. However, selective destruction of T lymphocytes and human AIDS-like disease phenotypes were not observed in F1 offspring. HIV-1 virus particles can be isolated from the affected F1 progeny and have the ability to infect human CD4-positive cells, but not murine fibroblasts.

　　(3) Comparative medicine HIV-1 has been confirmed as the pathogen of AIDS. Although the relationship between HIV-1 infection and the occurrence of AIDS is still unclear. Establishing an animal model of AIDS is an indispensable tool for studying immunodeficiency caused by HIV-1 and determining the efficacy of vaccines or the therapeutic effects of antiviral agents. So far, many animals such as chimpanzees, gibbons, rhesus monkeys, rabbits, cats, etc. have been tested in animal models of HIV-1 infection. However, due to the source of some large animals and economic reasons, HIV-1 animals There is no satisfactory report on the model. As an animal model, mice have received more and more attention from scholars from various countries. However, because mice do not have CD4 receptors, they cannot be used for HIV-1 research. In recent years. The successful research of genetically modified mice and severely combined immunodeficiency mice (SCID) makes it possible for mice to be used in the research of HIV-1, antiviral therapy of ADS, and animal models of vaccine efficacy.