Novel murine models for studying Cache Valley virus pathogenesis and in utero transmission.
Novel murine models for studying Cache Valley virus pathogenesis and in utero transmission.
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DOI：
10.1080/22221751.2021.1965497
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Auguste AJ
中科院分区：
文献类型：
--
作者：
López K;Wilson SN;Coutermash-Ott S;Tanelus M;Stone WB;Porier DL;Auguste DI;Muller JA;Allicock OM;Paulson SL;Erasmus JH;Auguste AJ
卡奇谷病毒(CVV)是一种流行的新出现的病原体，对北美的农业和人类健康具有重要意义。由于妊娠期间感染会导致严重的胚胎死亡，家畜出现可导致大量农业经济损失。虽然CVV的发病机制已经在反刍动物身上得到了很好的描述，但仍然没有小动物模型可用，这限制了我们研究其发病机制和进行临床前治疗试验的能力。在这里，我们探讨了CVV的发病机制、组织嗜性和各种小鼠模型的疾病结局，包括免疫功能正常和免疫受损的动物。我们的结果表明，小鼠CVV疾病的发展依赖于先天免疫反应，而I型干扰素信号对于预防小鼠感染是必不可少的。感染柯萨奇病毒的干扰素-αβR-/-小鼠表现出明显的疾病和致死性感染，与年龄相关的发病机制差异很小，表明该模型适合于与发病相关的以及短期和长期治疗研究。我们还开发了一种新的CVV宫内传播模型，该模型在感染期间显示出高传播率、自然流产和先天性畸形。CVV感染表现出广泛的组织嗜性，在肝、脾和胎盘组织中显著放大。具有免疫能力的小鼠通常对感染具有抵抗力，并且只有在年龄相关的方式下才会表现出疾病。鉴于北美地区的高血清阳性率，以及合格蚊媒在地理上的持续扩张，CVV的流行和流行性出现的风险很高，需要对这一重要病原体进行干预。
Cache Valley virus (CVV) is a prevalent emerging pathogen of significant importance to agricultural and human health in North America. Emergence in livestock can result in substantial agroeconomic losses resulting from the severe embryonic lethality associated with infection during pregnancy. Although CVV pathogenesis has been well described in ruminants, small animal models are still unavailable, which limits our ability to study its pathogenesis and perform preclinical testing of therapeutics. Herein, we explored CVV pathogenesis, tissue tropism, and disease outcomes in a variety of murine models, including immune -competent and -compromised animals. Our results show that development of CVV disease in mice is dependent on innate immune responses, and type I interferon signalling is essential for preventing infection in mice. IFN-αβR-/- mice infected with CVV present with significant disease and lethal infections, with minimal differences in age-dependent pathogenesis, suggesting this model is appropriate for pathogenesis-related, and short- and long-term therapeutic studies. We also developed a novel CVV in utero transmission model that showed high rates of transmission, spontaneous abortions, and congenital malformations during infection. CVV infection presents a wide tissue tropism, with significant amplification in liver, spleen, and placenta tissues. Immune-competent mice are generally resistant to infection, and only show disease in an age dependent manner. Given the high seropositivity rates in regions of North America, and the continuing geographic expansion of competent mosquito vectors, the risk of epidemic and epizootic emergence of CVV is high, and interventions are needed for this important pathogen.
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影响因子：
1.6
作者：
Brockus, CL;Grimstad, PR
通讯作者：
Grimstad, PR
影响因子：
5.9
作者：
Noronha, Leela E.;Wilson, William C.
通讯作者：
Wilson, William C.
影响因子：
2.1
作者：
Andreadis, Theodore G.;Armstrong, Philip M.;Main, Andrew J.
通讯作者：
Main, Andrew J.
DOI：
10.4269/ajtmh.1986.35.429
发表时间：
1986-03-01
影响因子：
3.3
作者：
CALISHER, CH;FRANCY, DB;MCLEAN, RG
通讯作者：
MCLEAN, RG
影响因子：
56.9
作者：
HOLDEN, P;HESS, AD
通讯作者：
HESS, AD