Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Virol. 2010 Aug;84(16):8172-80. doi: 10.1128/JVI.00621-10. Epub 2010 Jun 2.
Infection with monkeypox virus (MPXV) causes disease manifestations in humans that are similar, although usually less severe, than those of smallpox. Since routine vaccination for smallpox ceased more than 30 years ago, there is concern that MPXV could be used for bioterrorism. Thus, there is a need to develop animal models to study MPXV infection. Accordingly, we screened 38 inbred mouse strains for susceptibility to MPXV. Three highly susceptible wild-derived inbred strains were identified, of which CAST/EiJ was further developed as a model. Using an intranasal route of infection with an isolate of the Congo Basin clade of MPXV, CAST/EiJ mice exhibited weight loss, morbidity, and death in a dose-dependent manner with a calculated 50% lethal dose (LD(50)) of 680 PFU, whereas there were no deaths of BALB/c mice at a 10,000-fold higher dose. CAST/EiJ mice exhibited greater MPXV sensitivity when infected via the intraperitoneal route, with an LD(50) of 14 PFU. Both routes resulted in MPXV replication in the lung, spleen, and liver. Intranasal infection with an isolate of the less-pathogenic West African clade yielded an LD(50) of 7,600 PFU. The immune competence of CAST/EiJ mice was established by immunization with vaccinia virus, which induced antigen-specific T- and B-lymphocyte responses and fully protected mice from lethal doses of MPXV. The new mouse model has the following advantages for studying pathogenesis of MPXV, as well as for evaluation of potential vaccines and therapeutics: relative sensitivity to MPXV through multiple routes, genetic homogeneity, available immunological reagents, and commercial production.
感染猴痘病毒（MPXV）会导致人类出现类似于天花的疾病症状，但通常症状较轻。由于常规天花疫苗接种已经停止了 30 多年，因此人们担心 MPXV 可能被用于生物恐怖主义。因此，需要开发动物模型来研究 MPXV 感染。为此，我们筛选了 38 种近交系小鼠对 MPXV 的易感性。鉴定出三种高度易感的野生来源近交系，其中 CAST/EiJ 进一步发展为模型。使用鼻内途径感染刚果盆地分支的 MPXV 分离株，CAST/EiJ 小鼠表现出体重减轻、发病和死亡，呈剂量依赖性，计算得出的 50%致死剂量（LD(50)）为 680PFU，而 BALB/c 小鼠在 10000 倍更高的剂量下没有死亡。当通过腹腔途径感染时，CAST/EiJ 小鼠对 MPXV 的敏感性更高，LD(50)为 14PFU。两种途径均导致肺、脾和肝中 MPXV 的复制。通过鼻内感染致病性较低的西非分支分离株，LD(50)为 7600PFU。通过接种痘苗病毒使 CAST/EiJ 小鼠建立免疫能力，这诱导了抗原特异性 T 和 B 淋巴细胞反应，并完全保护小鼠免受致命剂量的 MPXV 感染。新的小鼠模型在研究 MPXV 发病机制方面具有以下优势，也可用于评估潜在的疫苗和治疗方法：通过多种途径对 MPXV 的相对敏感性、遗传同质性、可用的免疫试剂和商业生产。
