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HIV-1在M. Nemestrina更多 在新生动物中比在成年动物中更活跃。 我们因此 启动了一项实验，其中HIV-1在M. nemestrina 新生儿，预期病毒毒力将增加， 个通道好吗 用于传代实验的病毒在14 感染后7周， HIV-1lai和HIV-1NL 4 -3。 将该病毒接种到两个新生儿中， 感染后20周， 动物们来给另外两只新生的猕猴喂食。 免疫学和 病毒学数据表明，病毒复制变得更加致命， 但到目前为止，动物没有受到不良后果 免受感染 第一次传代后获得的病毒也被 显示在体外M中复制到更高滴度。Nemestrina细胞， 表明分子适应性。 为了阐明 HIV-1在M. nemestrina细胞，我们已经建立了一个 可以评估所有病毒复制步骤的系统 数量上。 我们发现，HIV-1的复制被阻断在 病毒进入的水平，并在稍后，核后易位，步骤。 这些数据帮助我们设计了一种分子工程HIV-1， 增强了M. nemestrina细胞。 资金 NIH拨款RR 00166。 Kimball，L.E.和Bosch，M.L.体外HIV-1 猕猴PBMC中的感染被阻断， 逆转录 J. Med. Primatol. 27：99-103，1998.