A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.
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DOI:
10.1371/journal.pntd.0006042
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发表时间:
2017-10
影响因子:
3.8
通讯作者:
Maes P
Maes P
中科院分区:
医学2区
文献类型:
--
作者:
Vergote V;Laenen L;Vanmechelen B;Van Ranst M;Verbeken E;Hooper JW;Maes P

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汉坦病毒是两种临床疾病的出血性病原体,在世界范围内发现,其严重程度、发病率和死亡率各不相同。最致命的汉他病毒发现于美洲大陆,其中最流行的病毒如安第斯山脉病毒和辛农布尔病毒已知会引起汉他病毒肺综合征。新世界汉坦病毒感染免疫活性仓鼠导致无症状感染,但安第斯山脉病毒和马波拉病毒除外;这是唯一在免疫活性叙利亚仓鼠中引起致死性疾病的汉坦病毒,类似于人类汉坦病毒肺综合征。用地塞米松和环磷酰胺免疫抑制的仓鼠肌内感染不同的新世界汉他病毒株(河口病毒、黑溪运河病毒、Caño Delgadito病毒、Choclo病毒、拉古纳内格拉病毒和Maporal病毒)。在目前的研究中,我们表明,免疫抑制仓鼠感染新世界汉他病毒的结果,在急性疾病,精确地模仿汉他病毒病在人类和安第斯山脉病毒感染的仓鼠。感染的仓鼠表现出特定的疾病临床体征,此外,肺组织的组织学分析显示肺水肿和肺泡隔内炎症的体征。在这项研究中,我们能够用不同的新世界汉他病毒感染免疫抑制的仓鼠,达到致命的结果,并出现类似人类疾病的疾病迹象。近年来,出血热病毒变得更加重要。这些病毒在日常环境中的更显著存在及其对全球健康的影响对研究这些病毒产生了积极影响。解决其疾病机制和干预其复制和相关健康负担的方法将在未来几十年内仍然是一个挑战。这一挑战也对汉坦病毒(一种新出现的人畜共患病)产生影响。没有疫苗或抗病毒治疗是世卫组织预先鉴定的,也没有显示出在人类中引起良好的保护性或治疗性抗病毒反应。其主要原因之一是缺乏良好的动物疾病模型和研究集中在这一主题。没有代表性的模型,很难研究新的潜在药物。在这种情况下,我们专注于建立一个疾病模型,最突出的新世界汉坦病毒。
Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease. Hemorrhagic fever viruses have become of much greater importance in recent years. The more prominent presence of these viruses in a day-to-day setting and their impact on global health has had a positive impact on studying these viruses. Resolving their disease mechanisms and ways to intervene in their replication and associated health burden will stay a challenge for the upcoming decades. This challenge also counts for hantavirus, an emerging zoonosis. No vaccine or antiviral treatment is WHO prequalified or has shown to elicit a good protective or therapeutic antiviral response in humans. One of the main reasons is the lack of good animal disease models and the research focusing on this topic. Without a representative model, it is difficult to investigate new potential drugs. Within this setting we focused on establishing a disease model for the most prominent New World hantaviruses.
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