Study of monkeypox virus in rodents

啮齿类动物猴痘病毒的研究

• 批准号: 6814371
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6814371
• 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）：Monkeypox，ORF和Molluscum Contagiosum病毒引起全球最常见的痘病毒感染。其中，猴蛋白酶病毒具有最大的潜力，可以作为自然感染或通过犯罪事件引起人口重大疾病。与天花不同的是，蒙基波病毒的人向人传播效率非常低，并且很少有三代以上的索引情况传播。随着1982年非洲撒哈拉以南地区天花疫苗接种计划的停止，以及人类对维持蒙基托病毒动物储层的人类侵占增加，这​​种病毒正在作为人类病原体重新出现。人类感染的频率增加为选择可以在人类种群中维持的基因型提供了机会，而无需定期重新引入动物储层。因此，Monkeypox病毒有可能成为滋扰人畜共患病。 2003年在中西部爆发人类猴子的爆发表明，关于该病毒的自然生物学及其引起人类疾病的潜力，我们了解了多少。从加纳进口到美国进口的非洲啮齿动物没有表现出蒙基毒病毒致死感染的预期迹象（例如结膜炎，淋巴结肿大和皮肤病变），但能够将疾病有效地传播给造成71例人类蒙基托克斯病例的草原犬。尽管已经对Simian Monkeypox进行了很多研究，但像人类一样的猴子被认为是偶然的宿主。在啮齿动物物种中，缺乏有关蒙基氧基病毒生物学的信息，而非洲可能充当天然储层。 该提案旨在研究易感啮齿动物物种中猴蛋白质病毒的生物学，这些物种将允许评估Monkeypox病毒的传播性，毒力和宿主范围。这些信息将有助于我们理解疾病的epizootic爆发。此外，由于人类蒙基托克斯与天花没有区别，因此一种概括天然疾病的小动物猴子模型可能会为我们提供对人类蒙基巨星和天花的见解。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提供当前小鼠和猴子模型之间的中间步骤，以评估疫苗和抗病毒药对天花的疗效。