IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN, ELDERLY, AND COMPROMISED POPULATIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 西尼罗河病毒（WNV）感染脑炎的风险随着年龄的增长而急剧增加。患有神经侵入性疾病的人在70岁以下的死亡率低于4%，之后死亡率上升到20%以上。我们在ONPRC的合作者用两种剂量的病毒（1 × 107或1 × 109 pfu/动物）攻击16只年龄恒河猴（17-30岁）和9只成年恒河猴（6-9岁）;一些实验包括从TNPRC的昆虫库中产生的蚊子唾液腺提取物（SGE）。此外，在胸腺切除术和/或CD 8 T细胞耗竭后，对15只食蟹猴进行激发，以测试各种水平的免疫缺陷。动物临床表现正常。没有发现可归因于西尼罗河病毒感染的发热、食欲改变或行为改变。全血的定量PCR显示离散和短暂的病毒血症;然而，从未分离出感染性病毒。先天性免疫应答的分析揭示了在感染后第2天和第10天之间单核细胞和嗜酸性粒细胞（具有SGE）的显著增加。此外，PBMC的流式细胞术分析显示CD 3-细胞的增殖增加。在获得性免疫方面，发现了与年龄相关的CD 4 + T细胞增殖的减少。几乎所有动物都出现并检测到了体液应答。结果表明，非人灵长类动物对西尼罗河病毒的攻击建立并保持有效的先天防御。

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. Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Individuals suffering neuroinvasive illness have mortality rates of less than 4% if under the age of 70, after which rates rise to over 20%. Our collaborators at ONPRC challenged sixteen age rhesus macagues (17-30 yrs) and 9 adult Rhesus (6-9 yrs) with two does of virus (1 x 107 or 1 x 109 pfu/animal); some experiments included mosquito salivary gland extract (SGE) generated from the insectory at TNPRC. Additionally fifteen Cynomolgus monkeys were challenged after thymectomy and/or CD8 T cell depletion to test various levels of immunodeficiency. Animals remained clinically normal. No fever, change in appetite, or behavior was detected that could be attributed to WNV infection. Quantitative PCR of whole blood revealed discrete and short lived viremia; however infectious virus was never isolated. Analysis of innate immune response revealed a marked increase in monocytes and eosinophils (with SGE) between days 2 and 10 post infection. Additionally flow cytometric analysis of PBMC revealed increased proliferation of CD3- cells. With regard to adaptive immunity, an age-associated reduction in CD4+ T cell proliferation was found. Humoral responses developed and were detected in nearly all animals. The results suggest that non-human primates mount and maintain an effective innate defense to WNV challenge.