ECOLOGY OF HANTAVIRUS ENZOOTICS: IMMUNE INTERVENTIONS

1993年农村严重呼吸道疾病暴发 美国西南部的居民是由于 一种以前未知的汉坦病毒，Sin Nombre病毒（SNV）。以及 在SNV在培养物中分离并且可以在病毒学上被分离之前， 表征，大量的RNA序列是可用的 从SNV基因组，并用于表征它的抗原性 并开发诊断测试。因此，SNV代表了一个优秀的 模式生物的情况下，快速发展和 可以使用人工设计的DNA疫苗， 干预由新出现的或不良的- 特征性病原体。事实上，我们对SNV是如何 是由其宿主鹿鼠携带的我们希望 研究SNV在鹿之间的传播机制 小鼠在野外环境中，并探讨免疫机制， SNV攻击的反应和保护， 小鼠和标准实验室小鼠（C57/B1）。 我们将在巡逻的情况下准备大型露天户外围栏， 位于新墨西哥州西部的偏远野生动物保护区 通过直接引入定义数量的 感染和未感染的鹿鼠，将配备 无线电发射器输入啮齿动物的人口统计学将是 仔细控制以调查传播途径他们的 外壳内的嵌套行为将由 无线电遥测和相关的传输效率， SNV。研究确定病毒污染的鸟巢 与传播有关的寝具也将进行。 鹿小鼠和C57/B1小鼠都将用于确定 使用裸DNA免疫的功效和免疫反应性 SNV的GI、G2和N基因。实验室老鼠将被用来 确定SNV基因组的哪些部分引起强B细胞 和T细胞反应，鹿鼠将被用于研究 防止SNV挑战。实验感染和 将使用现场传输挑战。我们的长期目标是 来建立鹿鼠种群 在自然环境中维持SNV感染，以鉴定遗传 可用于保护高危人群免疫策略 疫情中的人群，并确定如何破坏 SNV在鹿鼠之间的传播，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.