PATHOGENESIS OF SIV INFECTION OF NEONATAL RHESUS MACAQUES

新生恒河猴 SIV 感染的发病机制

• 批准号: 6591314
• 负责人: ANDREW A LACKNER
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591314
• 关键词: AIDS; Mammalia; bioimaging /biomedical imaging; communicable diseases; immunology; inflammation; infrared radiation; lymphatic system; mother /infant health care; nervous system; virus

HIV infection of children usually results in more rapid and severe disease than is seen in adults To explore the pathogenesis of pediatric AIDS we examined 20 rhesus macaques inoculated intravenously with SIV within 24 hours of birth Viral inocula included the pathogenic molecular clone SIVmac239 (n = 13), the macrophage-competent derivative SIVmac239/316 (n = 2), the minimally pathogenic SIVmac239 nef (n = 2) and uncloned SIVmac251 (n = 3) Infected neonates were sacrificed at intervals over the first 50 days (n = 16) or allowed to progress to terminal disease (n =4) Neonates inoculated with these viruses had higher viral loads than older animals inoculated with the same dose and stock of virus although differences did not reach statistical significance The highest viral loads were present in animals infected with SIVmac239 followed in order by SIVmac251, SIVmac239/316 and SIVmac239 nef The latter, were the only group of animals that showed normal weight gai n By in situ hybridization (ISH) virus was detectable in lymphoid tissues of all animals as early as 3 days postinoculation (dpi) with maximal numbers of infected cells by 14 dpi coincident with peak viremia The majority of infected cells were present in the T-cell zones of the spleen and lymph nodes and in the thymic medulla Rare, SIV-infected cells undergoing mitosis were also observed Combined in situ hybridization/immunohistochemistry experiments revealed that most of the infected cells were T-cells with little evidence of monocyte/macrophage infection Neonates infected with SIVmac239 nef had far fewer infected cells and they were primarily within germinal centers of the spleen and lymph nodes Histologically, spleen and lymph nodes of animals infected with SIVmac239 and SIVmac251 for < 50 days were characterized by an absence of follicular hyperplasia This is in contrast to older animals inoculated with these same viruses and age-matched neonates inoculated with eithe r SIVmac239/316 or SIVmac239 nef which had marked follicular hyperplasia and dysplasia In summary, while viral loads were not significantly different between neonates and older animals inoculated with the same stock and dose of virus, numerous other differences were observed that must be the result of age-specific host determinants

儿童的艾滋病毒感染通常会导致更快和更严重 疾病比成人探索的发病机理比 小儿辅助 SIV在24小时内出生病毒接力管之内包括 致病分子克隆SIVMAC239（n = 13）， 巨噬细胞的衍生衍生物SIVMAC239/316（n = 2），最小 致病SIVMAC239 NEF（n = 2）和未封闭的SIVMAC251（n = 3） 在最初的50天内以隔离为间隔感染的新生儿 （n = 16）或允许发展为终末疾病（n = 4）新生儿 接种这些病毒的病毒负荷比老年人更高 通过相同剂量和病毒量接种的动物，尽管 差异没有达到统计显着性最高的病毒意义 在感染SIVMAC239的动物中存在负载。 SIVMAC251，SIVMAC239/316和SIVMAC239 NEF的订单是 唯一表现出正常重量gai n的动物群 杂交（ISH）病毒在所有人的淋巴组织中均可检测到病毒 最早的动物（DPI）最早具有最大数量的动物 受感染的细胞与14 dPI与峰值病毒血症一致的大多数 被感染的细胞存在于脾的T细胞区域中， 淋巴结和胸腺中稀有的SIV感染细胞 还观察到有丝分裂的原位合并 杂交/免疫组织化学实验表明，大多数 感染的细胞是T细胞，几乎没有证据表明 单核细胞/巨噬细胞感染新生儿被SIVMAC239 NEF感染 受感染细胞的较少，主要在生发中 脾脏和淋巴结的中心在组织学上，脾和淋巴 感染SIVMAC239和SIVMAC251的动物节点<50天 以缺乏卵泡增生为特征 与接种这些相同病毒的老年动物形成鲜明对比， 年龄匹配的新生儿接种了R sivmac239/316或 SIVMAC239 NEF标记了卵泡增生和发育异常 摘要，虽然病毒载荷之间没有显着差异 新生儿和年龄较大的动物接种了相同的库存和剂量 病毒，观察到许多其他差异必须是 特定年龄特定宿主决定因素的结果