INFANT IMMUNOPROPHYLAXIS AGAINST A PRIMATE LENTIVIRUS

婴儿针对灵长类慢病毒的免疫预防

• 批准号: 8172331
• 负责人: Ruth Margrit Ruprecht
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172331
• 关键词: Acute; African; Animals; Blood Cells; Brain; Brain Diseases; CCR5 gene; CD8-Positive T-Lymphocytes; Cell Nucleus; Cells; Cerebrospinal Fluid; Chronic; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Funding; Genes; Genetic; Giant Cells; Grant; HIV; HIV-1; Human; Hybrids; Infant; Infection; Institution; Macaca mulatta; Macaca nemestrina; Microglia; Monkeys; Phase; Plasma; Primate Lentiviruses; Process; Research; Research Personnel; Resources; SIV; Source; Testing; United States National Institutes of Health; Viral Load result; Viremia; Virus; Virus Diseases; immunoprophylaxis; in vivo; novel; simian human immunodeficiency virus; viral RNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have constructed a novel simian-human immunodeficiency virus (SHIV), a hybrid virus that is part monkey AIDS virus (termed SIV), part human AIDS virus (termed HIV-1). This hybrid virus, SHIV-Bo159N4, encodes the envelope gene of a primary HIV-1 strain that was adapted in human brain-derived cells. Our new virus, SHIV-Bo159N4, replicated well in blood cells of all monkeys tested. Like the original HIV-1 strain from which we derived the envelope gene, our SHIV-Bo159N4 enters cells through a molecule called CCR5. Cells infected with our new virus form giant cells that contain many nuclei. To test whether SHIV-Bo159N4 can replicate in vivo, rhesus monkeys were inoculated intravenously and mucosally with this new virus; all had high viral RNA loads. To increase viremia in the acute phase, the CD8+ cells were depleted in some animals shortly after inoculation; high viral RNA levels were seen in plasma and cerebrospinal fluid (CSF). We have also inoculated pigtailed monkeys with SHIV-Bo159N4 under depletion of CD8+ cells; again, very high viral loads were observed in plasma and CSF. The animals with the highest CSF viral RNA loads were euthanized, microglia were isolated and transferred to new recipients. Brain sections are being tested for evidence of productive viral infection and brain disease. We are currently following 10 rhesus and 2 pigtailed monkeys with chronic infection for the development of disease. We have also constructed a second new SHIV that encodes the envelope gene of an African HIV-1 strain that is a genetic subtype (or Clade) A strain. This new Clade A SHIV is called SHIV-KNH1144. We are now in the process of adapting this new SHIV to replicate to high levels in rhesus monkeys. Two rhesus monkeys have already become systemically infected.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们已经构建了一种新型的猿猴 - 人类免疫缺陷病毒（SHIV），这是一种杂种病毒，是猴子艾滋病病毒（称为SIV）的一部分，是人类艾滋病病毒（称为HIV-1）。 该混合病毒SHIV-BO159N4编码了在人脑衍生细胞中适应的原代HIV-1菌株的包膜基因。 我们的新病毒SHIV-BO159N4在所有测试的猴子的血细胞中都很好地复制了。 就像我们得出包膜基因的原始HIV-1菌株一样，我们的SHIV-BO159N4通过称为CCR5的分子进入细胞。 感染我们新病毒的细胞，形成了许多含有许多核的巨细胞。为了测试Shiv-BO159N4是否可以在体内复制，将恒河猴与该新病毒持续接种和粘膜。所有都具有高病毒RNA负载。 为了增加急性期病毒血症，接种后不久，在某些动物中会耗尽CD8+细胞。在血浆和脑脊液（CSF）中观察到高病毒RNA水平。 在CD8+细胞耗竭的情况下，我们还与Shiv-BO159N4接种了辫子的猴子。同样，在血浆和CSF中观察到非常高的病毒载荷。 将CSF病毒RNA负荷的动物安乐死，分离出小胶质细胞并转移到新的受体中。正在测试脑部的生产性病毒感染和脑部疾病的证据。 目前，我们正在遵循10只恒河和2只辫子猴子，并慢性感染疾病。 我们还构建了第二个新的SHIV，该SHIV编码非洲HIV-1菌株的包络基因，该菌株是遗传亚型（或进化枝）菌株。 这个新的进化枝A SHIV称为Shiv-Knh1144。现在，我们正在调整这种新的SHIV以在恒河猴中复制到高水平。 两只恒河猴已经被系统地感染了。