Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible to Monkeypox Virus Infection for Use as Small Animal Models
Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible to Monkeypox Virus Infection for Use as Small Animal Models
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DOI：
10.1128/jvi.00621-10
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发表时间：
2010-08-15
影响因子：
5.4
通讯作者：
Earl, Patricia L.
中科院分区：
文献类型：
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作者：
Americo, Jeffrey L.;Moss, Bernard;Earl, Patricia L.
感染猴痘病毒(MPXV)在人类中引起的疾病表现与天花相似，但通常没有天花那么严重。由于30多年前停止了对天花的常规疫苗接种，人们担心MPXV可能被用于生物恐怖主义。因此，有必要建立动物模型来研究MPXV感染。因此，我们筛选了38个近交系小鼠对MPXV的易感性。鉴定出3个高度感病的野生自交系，其中CAST/EIJ是进一步发展的模式。使用鼻内感染MPXV刚果盆地分支分离株的方法，CAST/EIJ小鼠以剂量依赖的方式表现出体重减轻、发病率和死亡，计算的50%致死剂量(LD50)为680pfu，而BALB/c小鼠在10,000倍的剂量下没有死亡。CAST/EIJ小鼠在通过腹膜途径感染MPXV时表现出更高的敏感度，LD50为14pfu。这两种途径都导致MPXV在肺、脾和肝脏中复制。经鼻感染致病性较低的西非分支的一个分离物的半数致死量为7600 pfu。用痘苗病毒免疫CAST/EIJ小鼠，可诱导抗原特异性T、B淋巴细胞反应，并能完全保护小鼠免受MPXV致死剂量的攻击。新的小鼠模型在研究MPXV的发病机制以及评估潜在的疫苗和治疗方法方面具有以下优势：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化生产。
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 (LD50) 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 LD50 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 LD50 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.