Hantavirus-induced pathogenesis in mice with a humanized immune system
Hantavirus-induced pathogenesis in mice with a humanized immune system
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DOI：
10.1099/vir.0.000087
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发表时间：
2015-06-01
影响因子：
3.8
通讯作者：
Schoenrich, Guenther
中科院分区：
文献类型：
--
作者：
Kobak, Lidija;Raftery, Martin J.;Schoenrich, Guenther
汉坦病毒是一种新出现的人畜共患病原体，可引起人类严重疾病。临床观察表明，人类免疫成分有助于汉他病毒诱导的病理学。为了解决这个问题，我们产生了具有人源化免疫系统的小鼠。这些动物的汉坦病毒感染导致与体重减轻、活动减少、皮毛起皱和肺组织炎性浸润相关的全身感染。有趣的是，感染后，携带人类白细胞抗原（HLA）I类限制性人类CD8 + T细胞的人源化小鼠比HLA I类阴性人源化小鼠（第15天）更早（第10天）开始减轻体重。此外，在这些小鼠中，人类血小板的数量下降了77%，而中性血小板的数量没有变化，说明啮齿动物和人类血淋巴系统之间的差异可能有助于疾病的发展。据我们所知，这是第一次描述汉他病毒感染的人源化小鼠模型，我们的结果表明，汉他病毒的发病机制中的作用，人类免疫细胞。
Hantaviruses are emerging zoonotic pathogens that can cause severe disease in humans. Clinical observations suggest that human immune components contribute to hantavirus-induced pathology. To address this issue we generated mice with a humanized immune system. Hantavirus infection of these animals resulted in systemic infection associated with weight loss, decreased activity, ruffled fur and inflammatory infiltrates of lung tissue. Intriguingly, after infection, humanized mice harbouring human leukocyte antigen (HLA) class I-restricted human CD8 + T cells started to lose weight earlier (day 10) than HLA class I-negative- humanized mice (day 15). Moreover, in these mice the number of human platelets dropped by 77% whereas the number of nnurine platelets did not change, illustrating how differences between rodent and human haematolymphoid systems may contribute to disease development. To our knowledge this is the first description of a humanized mouse model of hantavirus infection, and our results indicate a role for human immune cells in hantaviral pathogenesis.