An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction
An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction
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DOI：
10.1073/pnas.161290298
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发表时间：
2001-07-31
影响因子：
11.1
通讯作者：
Bryant, J
中科院分区：
文献类型：
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作者：
Reid, W;Sadowska, M;Bryant, J
据我们所知，我们报告了第一只 HIV 1 型 (HIV-1) 转基因 (Tg) 大鼠。转基因的表达由具有功能性缺失 gag 和 pol 的 HIV-1 原病毒组成，受病毒长末端重复序列的调节。剪接和未剪接的病毒转录本在淋巴结、胸腺、肝脏、肾脏和脾脏中表达，表明 Tat 和 Rev 具有功能。通过免疫组织化学在脾组织切片中鉴定出病毒蛋白，并且 gp120 存在于脾巨噬细胞、T 细胞和 B 细胞以及血清中。临床症状包括消瘦、轻度至重度皮肤损伤、不透明白内障、神经系统症状和呼吸困难。组织病理学包括动脉周围淋巴鞘内脾细胞选择性丢失、内皮细胞和脾细胞凋亡增加、脾滤泡增生、肠系膜淋巴结淋巴细胞耗竭、间质性肺炎、银屑病皮肤病变以及神经、心脏和肾脏病理。免疫学上，对匙孔血蓝蛋白的迟发型超敏反应减弱。相比之下，抗体滴度和对回忆抗原（匙孔血蓝蛋白）的增殖反应均正常。因此，HIV-1 Tg 大鼠在病毒基因表达、免疫反应改变和感染引起的病理学方面与感染 HIV-1 的人类有许多相似之处。 HIV-1 Tg大鼠可能为慢性HIV-1疾病的一些致病表现提供有价值的模型，并且可用于测试针对原病毒整合后的病毒复制阶段的治疗方案。
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.