ECOLOGY OF HANTAVIRUS ENZOOTICS: IMMUNE INTERVENTIONS

汉坦病毒的生态学：免疫干预

• 批准号: 6171010
• 负责人: Brian L. Hjelle
• 金额: $ 26.09万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171010
• 关键词: B lymphocyte; Hantavirus; Peromyscus; T lymphocyte; animal breeding; antibody neutralization test; antigen antibody reaction; behavioral /social science research tag; cellular immunity; disease /disorder etiology; disease /disorder prevention /control; disease outbreaks; disease reservoirs; disease vectors; drug screening /evaluation; ecology; emerging infectious disease; enzyme linked immunosorbent assay; epizootiology; ethology; field study; laboratory mouse; nonhuman therapy evaluation; telemetry; tissue /cell culture; vector vaccine; western blottings

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.

1993年农村严重呼吸道疾病的爆发 美国西南部的居民是由于出现而引起的 以前未知的汉塔病毒，罪恶的nombre病毒（SNV）。出色地 在SNV在文化中孤立之前，可以在病毒学上 特征，大量的RNA序列可用 来自SNV基因组，用于抗原表征 并开发诊断测试。 SNV因此代表了一个极好的 模型有机体，以快速发展和 可以使用经验设计的DNA疫苗的部署 干预新出现或不良造成的爆发 表征病原体。几乎什么都不知道SNV 由其储层主机The Deer Mouse携带。我们希望 研究SNV在鹿中传播的机制 在现场设置中的小鼠并探索免疫机制 使用两只鹿的反应和保护免于SNV挑战 小鼠和标准实验室小鼠（C57/BL）。 我们将在巡逻中准备大型的露天户外围墙 新墨西哥州西部的远程野生动物保护区探索 通过直接引入定义的数量来传输SNV 感染和未感染的鹿小鼠，将配备 辐射递送器。输入啮齿动物的人口统计学将是 仔细控制以调查传输途径。他们的 围栏内的嵌套行为将由 radiotelemetry，与传播效率相关 SNV。研究确定病毒污染巢的研究 床上用品也将与传输有关。 鹿小鼠和C57/BL小鼠都将用于确定 使用使用裸体DNA免疫的功效和免疫反应性 SNV的GI，G2和N基因。实验室老鼠将习惯 确定SNV基因组的哪些部分会引起强B细胞 和T细胞的反应以及鹿小鼠将用于研究 防止SNV挑战。两者都是实验感染和 将使用现场传输挑战。我们的长期目标是 建立鹿小鼠种群的机制 在自然环境中保持SNV感染，以识别遗传 可以用来保护高危人类的免疫策略 爆发中的种群，并确定破坏的方法 SNV在鹿小鼠中的传播，从而设计 预防，控制和治疗策略。