A Susceptible Mouse Model for Zika Virus Infection.
A Susceptible Mouse Model for Zika Virus Infection.
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DOI：
10.1371/journal.pntd.0004658
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发表时间：
2016-05
影响因子：
3.8
通讯作者：
Hewson R
中科院分区：
文献类型：
--
作者：
Dowall SD;Graham VA;Rayner E;Atkinson B;Hall G;Watson RJ;Bosworth A;Bonney LC;Kitchen S;Hewson R
寨卡病毒（ZIKV）是一种由蚊子传播的病原体，近期已从非洲扩散到太平洋和南美洲地区。尽管1947年就首次被发现，但人们对该病毒知之甚少，而且其传播与吉兰 - 巴雷综合征和小头畸形病例的增加有关。目前尚无针对寨卡病毒感染的已知疫苗或抗病毒药物。评估干预措施的进展需要开发动物模型来测试功效；然而，关于体内研究的报道有限。唯一易感的小鼠模型涉及脑内接种或幼小动物，这并不能模拟自然感染。我们的报告研究了I型干扰素受体缺陷型（A129）小鼠以及其亲本品系（129Sv/Ev）在小腿皮下接种以模拟蚊子叮咬后感染寨卡病毒的效果。A129小鼠出现了严重症状，在血液、大脑、脾脏、肝脏和卵巢中都检测到广泛的病毒RNA。这些动物的组织学变化也很显著。129Sv/Ev小鼠没有出现临床症状或组织学变化，尽管在血液、脾脏和卵巢中可检测到病毒RNA，但其水平低于A129小鼠。我们的研究结果表明A129小鼠对寨卡病毒高度易感，因此A129小鼠代表了一种合适且急需的小动物模型，可用于疫苗和抗病毒药物的测试。
自1947年首次被发现以来，寨卡病毒（ZIKV）主要与一种症状包括轻度发热和皮疹的轻症疾病有关。2007年，该病毒从非洲传播到法属波利尼西亚，然后继续扩散到太平洋地区以及南美洲。在这些新地区，寨卡病毒与更严重的临床病症有关，包括吉兰 - 巴雷综合征（GBS）和小头畸形。目前没有经批准的对寨卡病毒有明确活性的抗病毒药物或疫苗，世界卫生组织宣布寨卡病毒的传播为国际关注的突发公共卫生事件。在此，我们使用了一种I型干扰素受体缺陷的小鼠品系（A129），并表明这些小鼠在接种后易感染寨卡病毒，这种接种方式与通过蚊子叮咬的自然感染途径非常相似。尽管A129小鼠先天性干扰素反应缺陷，但它们保留了适应性免疫，因此已成功地被用作疫苗和抗病毒药物测试的合适模型。我们的研究为未来针对寨卡病毒的干预措施测试提供了一种合适的小动物模型的详细信息。
Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies. The only susceptible murine models have involved intracerebral inoculations or juvenile animals, which do not replicate natural infection. Our report has studied the effect of ZIKV infection in type-I interferon receptor deficient (A129) mice and the parent strain (129Sv/Ev) after subcutaneous challenge in the lower leg to mimic a mosquito bite. A129 mice developed severe symptoms with widespread viral RNA detection in the blood, brain, spleen, liver and ovaries. Histological changes were also striking in these animals. 129Sv/Ev mice developed no clinical symptoms or histological changes, despite viral RNA being detectable in the blood, spleen and ovaries, albeit at lower levels than those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus A129 mice represent a suitable, and urgently required, small animal model for the testing of vaccines and antivirals. Since first being recognised in 1947, Zika virus (ZIKV) has mainly been associated with a mild illness with symptoms including a limited fever and rash. In 2007 the virus spread from Africa into French Polynesia and then onwards across Pacific regions and into South America. In these new regions, ZIKV has been associated with more severe clinical conditions including Gullain-Barre syndrome (GBS) and microcephaly. There are no currently approved antivirals or vaccines available with proven activity against ZIKV, and the World Health Organisation declared the spread of ZIKV as a Public Health Emergency of International Concern. Here, we have used a mouse strain with a deficiency in the type-I interferon receptor (A129) and shown that these mice are susceptible to ZIKV infection after an inoculation that closely resembles the natural route of infection via mosquito bite. Although A129 mice are deficient in the innate interferon response, they retain their adaptive immunity and thus have successfully been used as suitable models for the testing of vaccinations and antivirals. Our study provides details on a suitable small animal model for the testing of future interventions against ZIKV.