Role of Heat Shock Response in a Zoonotic Virus

热休克反应在人畜共患病毒中的作用

• 批准号: 6420238
• 负责人: Brian L. Hjelle
• 金额: $ 29万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6420238
• 关键词: Peromyscus; RNase protection assay; Sin Nombre virus; cold temperature; confocal scanning microscopy; corticosteroids; disease reservoirs; heat; heat shock proteins; heavy metals; hormone regulation /control mechanism; molecular cloning; nuclear runoff assay; phenylephrine; protein localization; temperature; virus antigen; virus diseases; virus replication; zoonosis

DESCRIPTION: (provided by the applicant): Deer mice (Peromyscus maniculatus) are the natural reservoirs for Sin Nombre (SN) Hantavirus, the cause of an often-fatal acute cardiorespiratory illness, Hantavirus cardiopulmonary syndrome (HCPS). HCPS is most common in the western United States, with more than 50 cases recorded in New Mexico alone. Minorities, especially American Indians, and the poor are especially affected. Virtually nothing is known of how SN virus is maintained in wild rodents, and thus it is very difficult to predict outbreaks or to prevent spread of the virus in the wild. The virus is spread among adult wild rodents and despite being locally extinct at times, it dramatically increase to infect up to 50 percent of the mice in a population. Deer mice develop lifelong infection after exposure, but after about 60 days the virus is vastly diminished, with residual low levels of viral expression can be found primarily in the heart, lungs, and brown adipose tissue (BAT). SN virus has evolved some mysterious means by which it can reactivate in a population in response to seasonal influences, and that reactivation leads to spread among mice. Recently we found that cold stress may cause a reactivation of viral infection in deer mice. This finding suggests that the virus may be using the host?s normal stress response to support reactivation. To pursue this further we propose to determine (1) how stress responses promote the reactivation of hantaviruses in the laboratory; (2) what events cause hantaviruses to reactivate in deer mice; and (3) the molecular interactions that lead to the activation of the virus in infected cells and animals. This study will open a new window of study of the mechanisms of maintenance of persistent viral infections in populations, and will have special relevance to zoonotic RNA virus diseases such as those caused by hantaviruses, arenaviruses such as Lassa, Ebola virus and rabies virus.

描述：（由申请人提供）：鹿小鼠（Peromyscus maniculatus） 是罪恶nombre（sn）hantavirus的天然储藏 通常致命的急性心肺疾病，汉坦病毒心肺 综合征（HCP）。 HCP在美国西部最常见，有更多 仅在新墨西哥州就记录了50例。少数民族，尤其是美国人 印第安人和穷人尤其受到影响。几乎什么都不知道 如何在野生啮齿动物中保持SN病毒，因此很难很难 预测暴发或防止病毒在野外传播。病毒是 散布在成年野生啮齿动物中，尽管有时是局部灭绝的，但 在人群中最多增加了50％的小鼠。 鹿小鼠在暴露后发展终生感染，但大约60天后 该病毒大大减少，残留的病毒表达水平较低 可以主要在心脏，肺部和棕色脂肪组织（BAT）中找到。 sn 病毒已经发展出了一些神秘的手段，它可以在 响应季节性影响的人口，重新激活导致 散布在小鼠中。最近，我们发现冷应力可能引起重新激活 鹿小鼠病毒感染。这一发现表明该病毒可能是 使用宿主的正常应力反应来支持重新激活。追求这一点 此外，我们建议（1）压力反应如何促进 实验室中汉坦病毒的重新激活； （2）导致什么事件 汉坦病毒在鹿小鼠中重新激活； （3）分子相互作用 这导致感染细胞和动物中病毒的激活。 这项研究将为维护机制的新窗口开辟一个新的研究窗口 人群中持续的病毒感染，并将与 人畜共动性RNA病毒疾病，例如由汉坦病毒引起的疾病 例如LASSA，埃博拉病毒和狂犬病病毒。