Study of monkeypox virus in rodents

描述(由申请人提供)：猴痘、ORF和传染性软骨病病毒引起全世界最频繁的痘病毒感染。在这些病毒中，猴痘病毒最有可能作为自然感染或通过犯罪事件在人类群体中引起重大疾病。与天花不同，猴痘病毒在人与人之间传播的效率很低，一个指示病例很少有超过三代的传播。随着1982年非洲撒哈拉以南地区天花疫苗接种计划的停止，以及人类入侵维持猴痘病毒动物宿主的栖息地的增加，这种病毒正重新成为人类的病原体。人类感染频率的增加为选择可以在人类种群中保持的基因类型提供了机会，而不需要从动物储藏室定期重新引入。因此，猴痘病毒有可能不仅仅成为一种令人讨厌的人畜共患病。 2003年在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可能性知之甚少。从加纳进口到美国的非洲啮齿动物没有表现出预期的猴痘病毒致命感染迹象(例如结膜炎、淋巴结病和皮肤病变)，但能够有效地将疾病传播给草原犬，这些草原犬是71例人类猴痘的罪魁祸首。虽然已经对猴痘做了很多研究，但猴子和人类一样被认为是偶然的宿主。缺乏关于猴痘病毒在非洲可能作为天然宿主的啮齿动物物种中的生物学信息。 这项建议旨在研究猴痘病毒在易感啮齿动物物种中的生物学，以便能够评估猴痘病毒的传播力、毒力和宿主范围。这些信息将有助于我们了解流行性疾病的爆发。此外，由于人类猴痘和天花难以区分，一个重现自然疾病的小动物猴痘模型可能会为我们提供对人类猴痘和天花的洞察。最后，一个在低剂量病毒(102pfu)下产生暴发性致命感染的小动物模型可以为评估疫苗和抗病毒药物对天花的疗效提供一个介于当前小鼠和猴子模型之间的中间步骤。

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.