Can non-human primates serve as models for investigating dengue disease pathogenesis?
Can non-human primates serve as models for investigating dengue disease pathogenesis?
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DOI：
10.3389/fmicb.2013.00305
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发表时间：
2013-10-11
影响因子：
5.2
通讯作者：
Villinger F
中科院分区：
文献类型：
--
作者：
Clark KB;Onlamoon N;Hsiao HM;Perng GC;Villinger F
登革热病毒 (DV) 感染全球 50 至 1 亿人，造成公共卫生损失总计数十亿美元。它是登革热 (DF) 和登革出血热/登革休克综合征 (DHF/DSS) 的病原体，这些媒介传播的疾病最初在热带地区占主导地位。由于其蚊媒伊蚊的扩张，DV 日益成为一个全球性问题。感染者可能会出现多种症状，从轻微发热到危及生命的疾病，其中可能包括血小板减少、白细胞减少、肝肿大、出血、血浆渗漏和休克。由于能够诱发经典人类病理学的动物模型有限，解释这些症状的根本机制受到了阻碍。目前，已有几种对适应性DV毒株敏感的非人灵长类动物（NHP）物种和小鼠品种。尽管病毒复制发生在这些动物身上，但它们都没有概括人类症状学的主要特征，在 NHP 中偶尔观察到疾病。最近，我们小组用印度恒河猴建立了 DV 血清型 2 静脉感染模型，该模型在初次接触病毒后可靠地产生皮肤出血。进一步操纵实验参数（病毒株、免疫细胞扩增、耗竭等）可以完善该模型并扩展其与人类 DF 的相关性。未来的目标包括应用该模型来阐明预先存在的免疫力对继发感染和免疫发病机制的作用。值得注意的是，即使使用我们的模型，灵长类动物体内和体外的病毒滴度也始终比人类体内的病毒滴度低 1000 倍。我们认为，只有在更高的病毒载量下才能实现能够证明严重发病机制的改进模型。尽管如此，我们的 DV 凝血病模型对于研究选定的病理机制以及测试 DV 候选药物和疫苗很有价值。
Dengue Virus (DV) infects between 50 and 100 million people globally, with public health costs totaling in the billions. It is the causative agent of dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), vector-borne diseases that initially predominated in the tropics. Due to the expansion of its mosquito vector, Aedes spp., DV is increasingly becoming a global problem. Infected individuals may present with a wide spectrum of symptoms, spanning from a mild febrile to a life-threatening illness, which may include thrombocytopenia, leucopenia, hepatomegaly, hemorrhaging, plasma leakage and shock. Deciphering the underlining mechanisms responsible for these symptoms has been hindered by the limited availability of animal models that can induce classic human pathology. Currently, several permissive non-human primate (NHP) species and mouse breeds susceptible to adapted DV strains are available. Though virus replication occurs in these animals, none of them recapitulate the cardinal features of human symptomatology, with disease only occasionally observed in NHPs. Recently our group established a DV serotype 2 intravenous infection model with the Indian rhesus macaque, which reliably produced cutaneous hemorrhages after primary virus exposure. Further manipulation of experimental parameters (virus strain, immune cell expansion, depletion, etc.) can refine this model and expand its relevance to human DF. Future goals include applying this model to elucidate the role of pre-existing immunity upon secondary infection and immunopathogenesis. Of note, virus titers in primates in vivo and in vitro, even with our model, have been consistently 1000-fold lower than those found in humans. We submit that an improved model, capable of demonstrating severe pathogenesis may only be achieved with higher virus loads. Nonetheless, our DV coagulopathy disease model is valuable for the study of select pathomechanisms and testing DV drug and vaccine candidates.
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影响因子：
3.7
作者：
Akkina R
通讯作者：
Akkina R
影响因子：
2.7
作者：
Alagarasu, K.;Mulay, A. P.;Cecilia, D.
通讯作者：
Cecilia, D.
DOI：
10.2987/8756-971x(2005)21
发表时间：
2005-09-01
影响因子：
1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Guzman, Maria G.
影响因子：
4.9
作者：
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通讯作者：
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