Study of monkeypox virus in rodents

啮齿类动物猴痘病毒的研究

• 批准号: 6911687
• 负责人: Robert MARK Buller
• 金额: $ 29.4万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911687
• 关键词: Poxviridae; aerosols; communicable disease transmission; disease /disorder etiology; disease /disorder model; enzyme linked immunosorbent assay; epizootiology; histopathology; host organism interaction; immunocytochemistry; laboratory rat; model design /development; squirrel; vaccine evaluation; viral vaccines; virulence; virus infection mechanism; virus replication; zoonosis

DESCRIPTION (provided by applicant): Monkeypox, orf, and molluscum contagiosum viruses cause the most frequent poxvirus infections worldwide. Of these, monkeypox virus has the greatest potential to cause significant disease in human populations either as a natural infection or through a criminal event. Unlike smallpox, person-to-person transmission of monkeypox virus is very inefficient, and there is rarely more than three generations of transmission from an index case. With cessation of the smallpox vaccination program in the Sub-Saharan region of Africa in 1982, and the increased encroachment of humans into habitat maintaining animal reservoirs of monkeypox virus, this virus is reemerging as a human pathogen. Increased frequency of human infections provides the opportunity for selection of genotypes that can be maintained in human populations without the necessity of periodic reintroductions from animal reservoirs. Thus monkeypox virus has the potential to become more than a nuisance zoonosis. The 2003 outbreak of human monkeypox in the Midwest indicated how little we know concerning the natural biology of this virus, and its potential to cause human disease. African rodents imported from Ghana into the U.S. showed none of the expected signs of a lethal infection with monkeypox virus (e.g. conjunctivitis, lymphadenopathy and skin lesions) yet were able to efficiently transmit the disease to prairie dogs that were responsible for 71 cases of human monkeypox. Although much research has been done on simian monkeypox, the monkey like the human is thought to be an incidental host. There is a lack of information on monkeypox virus biology in rodent species that in Africa may act as natural reservoirs. This proposal is aimed at studying the biology of monkeypox virus in susceptible rodent species that will permit the evaluation of monkeypox virus transmissibility, virulence, and host range. This information will contribute to our understanding of epizootic outbreaks of disease. Furthermore, since human monkeypox is indistinguishable from smallpox, a small animal monkeypox model that recapitulates natural disease may provide us with insights into human monkeypox and smallpox. And finally, a small animal model that yields a fulminant lethal infection at low doses of virus (<102 PFU) could provide an intermediate step between current mouse and monkey models for evaluation of the efficacy of vaccines and antivirals against smallpox.

描述（由申请人提供）：猴痘、orf 和传染性软疣病毒引起全世界最常见的痘病毒感染。其中，猴痘病毒最有可能作为自然感染或通过犯罪事件在人群中引起重大疾病。与天花不同，猴痘病毒的人际传播效率非常低，指示病例的传播很少超过三代。随着 1982 年非洲撒哈拉以南地区天花疫苗接种计划的停止，以及人类对猴痘病毒栖息地维持动物储存库的不断侵扰，这种病毒重新成为人类病原体。人类感染频率的增加为选择可以在人群中维持的基因型提供了机会，而无需定期从动物宿主中重新引入。因此，猴痘病毒有可能不仅仅是一种令人讨厌的人畜共患病。 2003 年中西部爆发的人类猴痘表明，我们对这种病毒的自然生物学及其引起人类疾病的潜力知之甚少。从加纳进口到美国的非洲啮齿动物没有表现出任何预期的猴痘病毒致命感染迹象（例如结膜炎、淋巴结肿大和皮肤损伤），但却能够有效地将疾病传播给草原土拨鼠，而草原土拨鼠是造成 71 例人类猴痘病例的原因。尽管对猿猴痘进行了大量研究，但猴子和人类一样被认为是偶然宿主。缺乏关于非洲可能作为天然宿主的啮齿动物物种中猴痘病毒生物学的信息。 该提案旨在研究易感啮齿类动物中猴痘病毒的生物学，从而评估猴痘病毒的传播性、毒力和宿主范围。这些信息将有助于我们了解动物流行病的爆发。此外，由于人类猴痘与天花无法区分，因此重现自然疾病的小动物猴痘模型可以为我们提供对人类猴痘和天花的深入了解。最后，在低剂量病毒（<102 PFU）下产生暴发性致死感染的小动物模型可以为当前小鼠和猴子模型之间的中间步骤提供一个中间步骤，用于评估疫苗和抗病毒药物对天花的功效。