Ebola Virus Transmission in Guinea Pigs
Ebola Virus Transmission in Guinea Pigs
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DOI：
10.1128/jvi.02836-14
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发表时间：
2015-01-01
影响因子：
5.4
通讯作者：
Kobinger, Gary P.
中科院分区：
文献类型：
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作者：
Wong, Gary;Qiu, Xiangguo;Kobinger, Gary P.
埃博拉病毒(EBOV)目前的传播特征不佳，被认为主要通过直接接触传染性物质而发生；然而，已有文献证明猪通过呼吸道传播给非人类灵长类动物。为了建立EBOV传播模型以进行有统计学意义的研究，对6只豚鼠(GPS)进行鼻内激发(I.N.)。或腹膜内注射(I.P.)10,000倍的GP适应的EBOV的50%致死剂量(LD)，然后引入幼稚的GPS作为笼友，在感染后1天接触暴露(P.I.)。这些动物被监测存活情况和疾病的临床体征，并在暴露后对病毒脱落进行定量。评估了幼稚GPS与受感染动物接触的时间变化对传播效率的影响。来自I.N的传播比来自I.P.挑战的GPS更有效，分别有17%和83%的幼稚GPS在暴露中存活。在P.I.第3天开始检测到病毒脱落。来自免疫缺陷和免疫缺陷的动物。接触时间与传播效率呈正相关，如果笼子中没有传染性动物床垫，通过架设钢丝网消除感染动物与幼年动物之间的直接接触是有效阻止病毒传播的。组织病理学和免疫组织化学结果显示，感染I.N.N的GPS表现出增强的肺部病理和气管中的EBOV抗原，这支持这些动物的病毒传播增加。结果表明，与系统感染的同类动物相比，I.N.N感染的GPS对幼小动物的传染性更强，传播是通过直接接触传染性物质发生的，包括那些通过短距离空气传播的物质。埃博拉病毒通常被认为通过传染性体液在人与人之间传播。然而，一项研究表明，埃博拉病毒可以在没有直接接触的情况下从猪传播到猴子。进一步的研究受到了阻碍，因为目前还没有经济的埃博拉传播动物模型。为了解决这个问题，我们建立了一个豚鼠传播模型，并确定了病毒传播背后的机制。存活数据，加上肺部和气管切片的显微镜检查，表明豚鼠黏膜感染是埃博拉传播的有效模型。与受感染动物接触的时间越长，病毒的传播就会增加，即使受感染的动物与幼稚的宿主没有直接接触，病毒传播也是可能的，但如果没有传染性物质，就可以阻止病毒传播。这些结果值得考虑，以制定未来预防埃博拉传播的战略，并更好地了解病毒传播所涉及的参数。
Ebola virus (EBOV) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (LD) of gp-adapted EBOV, and naive gps were then introduced as cage mates for contact exposure at 1 day postinfection (p.i.). The animals were monitored for survival and clinical signs of disease and quantitated for virus shedding postexposure. Changes in the duration of contact of naive gps with infected animals were evaluated for their impact on transmission efficiency. Transmission was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83% of naive gps surviving exposure, respectively. Virus shedding was detected beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naive animals through the erection of a steel mesh was effective at stopping virus spread, provided that infectious animal bedding was absent from the cages. Histopathological and immunohistochemical findings show that i.n.-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which supports increased virus transmission from these animals The results suggest that i.n.-challenged gps are more infectious to naive animals than their systemically infected counterparts and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances.IMPORTANCEEbola is generally thought to be spread between humans though infectious bodily fluids. However, a study has shown that Ebola can be spread from pigs to monkeys without direct contact. Further studies have been hampered, because an economical animal model for Ebola transmission is not available. To address this, we established a transmission model in guinea pigs and determined the mechanisms behind virus spread. The survival data, in addition to microscopic examination of lung and trachea sections, show that mucosal infection of guinea pigs is an efficient model for Ebola transmission. Virus spread is increased with longer contact times with an infected animal and is possible without direct contact between an infected and a naive host but can be stopped if infectious materials are absent. These results warrant consideration for the development of future strategies against Ebola transmission and for a better understanding of the parameters involved in virus spread.