Study of monkeypox virus in rodents

描述（由申请方提供）：猴痘、羊口疮和传染性软疣病毒是全球最常见的痘病毒感染。其中，猴痘病毒作为自然感染或通过犯罪事件在人群中引起重大疾病的可能性最大。与天花不同，猴痘病毒的人际传播效率很低，从一个指示病例开始，很少有超过三代的传播。随着1982年撒哈拉以南非洲地区天花疫苗接种计划的停止，以及人类对维持猴痘病毒动物宿主栖息地的入侵增加，该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年在中西部爆发的人猴痘表明，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预期的猴痘病毒致命感染的迹象（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鼠，这些草原犬鼠造成了71例人类猴痘病例。尽管对猿类猴痘已经做了很多研究，但猴子和人类一样被认为是偶然的宿主。在非洲，啮齿动物物种可能是猴痘病毒的天然储存库，但缺乏关于啮齿动物物种中猴痘病毒生物学的信息。 该提案旨在研究猴痘病毒在易感啮齿动物物种中的生物学，从而可以评价猴痘病毒的传播性、毒力和宿主范围。这一信息将有助于我们了解动物流行性疾病的爆发。此外，由于人类猴痘与天花无法区分，因此一种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模型之间的中间步骤，用于评估疫苗和抗病毒药物对天花的有效性。

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.