ECOLOGY OF HANTAVIRUS ENZOOTICS: IMMUNE INTERVENTIONS

1993年农村严重呼吸道疾病暴发疫情 美国西南部的居民是由病毒的出现引起的 一种以前不为人知的汉坦病毒，辛诺布雷病毒(SNV)。井 在SNV在培养中分离出来并可能在病毒学上 经鉴定，可获得大量的RNA序列 从SNV基因组中分离出来，并用于抗原性鉴定 并开发诊断测试。因此，SNV代表了一种极好的 模式生物体，用于快速发展和 可以使用经验性设计的DNA疫苗的部署 干预由新出现的或不好的- 具有病原体特征的。关于SNV是如何产生的，我们几乎一无所知 是由它的宿主鹿鼠携带的。我们希望 新城疫病毒在鹿间传播机制的研究 在野外环境下对小鼠的免疫机制进行探讨 对SNV挑战的反应和保护，使用两只鹿 小鼠和标准实验小鼠(C57/Bl)。 我们将在一个有巡逻的， 新墨西哥州西部偏远野生动物保护区探险 通过直接引入定义数量的SNV传输 感染和未感染的鹿小鼠，将安装 无线电发射机。输入啮齿动物的人口统计数据将是 仔细控制以调查传播途径。他们的 围栏内的嵌套行为将由 无线电遥测及其与传输效率的相关性 SNV.研究确定被病毒污染的鸟巢 与床上用品有关的传输也将进行。 鹿小鼠和C57/Bl小鼠都将被用来确定 裸露DNA疫苗的免疫效力和免疫反应性 SNV的GI、G2和N基因。实验室小鼠将被用来 确定SNV基因组的哪些部分能激发强大的B细胞 和T细胞反应，以及鹿鼠将被用来研究 防止SNV挑战。无论是实验性感染还是 将使用现场传输挑战。我们的长期目标是 为了建立鹿鼠种群的机制 在自然环境中保持SNV感染，以确定遗传 可用于保护高危人群的免疫策略 疫情中的人口，并找出扰乱 SNV在鹿小鼠中的传播，从而设计 预防、控制和治疗策略。

A 1993 outbreak of severe respiratory disease among rural residents of the southwestern US was caused by the emergence of a previously-unknown hantavirus, Sin Nombre virus (SNV). Well before SNV was isolated in culture and could be virologically characterized, large amounts of RNA sequence were available from the SNV genome, and used to characterize it antigenically and to develop diagnostic tests. SNV thus represents an excellent model organism for situations in which rapid development and deployment of empirically-designed DNA vaccines could be used to intervene in an outbreak caused by newly-emerged or poorly- characterized pathogens. Virtually nothing is known of how SNV is carried by its reservoir host, the deer mouse. We wish to investigate the mechanisms of transmission of SNV among deer mice in a field setting and to explore mechanisms of immune responses and protection from SNV challenge, using both deer mice and standard laboratory mice (C57/Bl). We will prepare large open-air outdoor enclosures on a patrolled, remote wildlife refuge in western New Mexico to explore transmission of SNV by directly introducing a defined number of infected and uninfected deer mice, which will be fitted with radiotransmitters. The demographics of input rodents will be carefully controlled to investigate the routes of transmission. Their nesting behavior within the enclosure will be monitored by radiotelemetry and correlated with efficiency of transmission of SNV. Studies to determine whether virus-contaminated nest bedding is associated with transmission will also be conducted. Both deer mice and C57/Bl mice will be used to determine the efficacy and immune reactivity to naked DNA immunization using the GI, G2, and N genes of SNV. Lab mice will be used to determine what portions of the SNV genome elicit strong B-cell and T-cell responses, and deer mice will be used to study protection against SNV challenge. Both experimental infection and field transmission challenges will be used. Our long-term goals are to establish the mechanisms by which deer mouse populations maintain SNV infection in natural settings, to identify genetic immunization strategies that may be used to protect at-risk human populations in an outbreak, and to identify ways to disrupt the transmission of SNV among deer mice, and thus to design prevention, control, and treatment strategies.