INFECTION OF M NEMESTRINA NEONATES W/ HIV 1

新生儿感染 HIV 1

• 批准号: 6219640
• 负责人: MARNIX L BOSCH
• 金额: $ 12.74万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219640
• 关键词: AIDS; Mammalia; animal tissue; communicable diseases; immunology; inflammation; lymphatic system; model design /development; sexually transmitted diseases; virus

We have found that replication of HIV-1 in M. nemestrina is more vigorous in neonates than in adult animals. We have therefore initiated an experiment in which HIV-1 is passaged in M. nemestrina neonates with the expectation that viral virulence will increase in passage. The virus used for the passage experiment was isolated at 14 weeks postinfection from a neonate that was infected with a mixture of HIV-1lai and HIV-1NL4-3. This virus was inoculated into two neonates, and then, at 20 weeks postinfection, virus was isolated from these two animals to inoculate two more neonatal macaques. Immunological and virological data indicate that viral replication became more virulent during passage, but that so far the animals suffer no ill consequences from infection. The virus obtained after the first passage was also shown to replicate to higher titers in vitro in M. nemestrina cells, suggesting molecular adaptation. In an attempt to elucidate blocks for HIV-1 replication i n M. nemestrina cells we have established a system in which all the viral replication steps can be assessed quantitatively. We found that HIV-1 replication is blocked at the level of viral entry and at a later, postnuclear translocation, step. These data help us to design a molecularly engineered HIV-1 with enhanced replication characteristics in M. nemestrina cells. FUNDING NIH grant RR00166. Kimball, L.E. and Bosch, M.L. In vitro HIV-1 infection in Macaca nemestrina PBMCs is blocked at a step beyond reverse transcription. J. Med. Primatol. 27:99-103, 1998.

我们发现M. Nemestrina中HIV-1的复制更多是 在新生儿中比成年动物剧烈。 因此，我们有 启动了一个实验，其中HIV-1在Nemestrina M. Nemestrina中被传递 新生儿期望病毒性毒力会增加 通道。 在14处分离用于通道实验的病毒 感染后的几周是从新生儿感染的，该新生儿被感染的混合物 HIV-1LAI和HIV-1NL4-3。 该病毒被接种到两个新生儿， 然后，感染后20周，从这两种病毒中分离出病毒 动物接种另外两个新生儿猕猴。 免疫学和 病毒学数据表明病毒复制变得更加毒 在通过期间，但到目前为止，动物没有遭受不良后果 从感染中。 第一次通过后获得的病毒也是 显示出在M. nemestrina细胞中复制到较高的体外滴度， 提示分子适应。 试图阐明块 对于HIV-1复制，N。Nemestrina细胞我们已经建立了A 可以评估所有病毒复制步骤的系统 定量。 我们发现HIV-1复制在 病毒输入水平以及后来的核后易位，步骤。 这些数据有助于我们使用 Nemestrina细胞中增强的复制特性。 资金 NIH授予RR00166。 Kimball，L.E。和Bosch，M.L。体外HIV-1 Macaca Nemestrina PBMC中的感染在超出一步 逆转录。 J. Med。 Primatol。 27：99-103，1998。