A bovine respiratory syncytial virus model with high clinical expression in calves with specific passive immunity.
A bovine respiratory syncytial virus model with high clinical expression in calves with specific passive immunity.
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DOI：
10.1186/s12917-015-0389-6
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发表时间：
2015-03-25
影响因子：
2.6
通讯作者：
Valarcher JF
中科院分区：
文献类型：
--
作者：
Blodörn K;Hägglund S;Gavier-Widen D;Eléouët JF;Riffault S;Pringle J;Taylor G;Valarcher JF
牛呼吸道合胞体病毒（BRSV）是全球牛呼吸道疾病的主要病因。犊牛尤其易受影响，即使其体内母源来源的牛呼吸道合胞体病毒特异性抗体（MDA）水平较低至中等也是如此。现有的牛呼吸道合胞体病毒疫苗对具有母源抗体的犊牛效果欠佳，而且针对这一目标群体已发表的感染模型缺乏临床症状表现。在此，我们对这样一个模型进行了完善和描述。
在第一个实验中，将两组各3头具有低水平母源抗体的犊牛通过吸入雾化的牛呼吸道合胞体病毒进行实验性接种，所接种的病毒分别为：在无菌犊牛中传代的斯努克毒株（BRSV - Snk），以及在细胞培养中传代的丹麦9402022号分离株（BRSV - Dk）。所有犊牛都出现了呼吸道疾病的临床症状，并排出高滴度的病毒，但BRSV - Snk引发的疾病更为严重，随后在第二个实验中，在5头具有中等水平母源抗体的犊牛身上重现了这一结果。这5头犊牛排出高滴度病毒，出现严重的疾病临床症状以及大面积的肺部宏观病变（平均±标准差，肺部的48.3±12.0%），伴有炎症细胞向肺部的浸润，其特征为分泌干扰素γ，并对肺功能有显著影响。
我们提出了一个牛呼吸道合胞体病毒感染模型，该模型在具有低至中等水平牛呼吸道合胞体病毒特异性母源抗体的幼龄犊牛中始终具有较高的临床症状表现，这可能在疾病发病机制研究或疫苗及抗病毒药物评估中有用。此外，还描述了用于评估牛呼吸道合胞体病毒感染结果的改进工具，包括肺功能的被动测量以及一个用于对疾病临床症状进行评分的改进系统。利用这种同源宿主犊牛模型，或许还能为有关人呼吸道合胞体病毒（HRSV）这一全球儿童发病的主要病因的一些难以解答的问题提供答案。
Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide. Calves are particularly affected, even with low to moderate levels of BRSV-specific maternally derived antibodies (MDA). Available BRSV vaccines have suboptimal efficacy in calves with MDA, and published infection models in this target group are lacking in clinical expression. Here, we refine and characterize such a model. In a first experiment, 2 groups of 3 calves with low levels of MDA were experimentally inoculated by inhalation of aerosolized BRSV, either: the Snook strain, passaged in gnotobiotic calves (BRSV-Snk), or isolate no. 9402022 Denmark, passaged in cell culture (BRSV-Dk). All calves developed clinical signs of respiratory disease and shed high titers of virus, but BRSV-Snk induced more severe disease, which was then reproduced in a second experiment in 5 calves with moderate levels of MDA. These 5 calves shed high titers of virus and developed severe clinical signs of disease and extensive macroscopic lung lesions (mean+/−SD, 48.3+/−12.0% of lung), with a pulmonary influx of inflammatory cells, characterized by interferon gamma secretion and a marked effect on lung function. We present a BRSV-infection model, with consistently high clinical expression in young calves with low to moderate levels of BRSV-specific MDA, that may prove useful in studies into disease pathogenesis, or evaluations of vaccines and antivirals. Additionally, refined tools to assess the outcome of BRSV infection are described, including passive measurement of lung function and a refined system to score clinical signs of disease. Using this cognate host calf model might also provide answers to elusive questions about human RSV (HRSV), a major cause of morbidity in children worldwide.
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影响因子：
5.5
作者：
Hägglund S;Hu K;Vargmar K;Poré L;Olofson AS;Blodörn K;Anderson J;Ahooghalandari P;Pringle J;Taylor G;Valarcher JF
通讯作者：
Valarcher JF
影响因子：
1.8
作者：
Grell, SN;Tjornehoj, K;Heegaard, PMH
通讯作者：
Heegaard, PMH
影响因子：
1.8
作者：
KIMMAN, TG;WESTENBRINK, F;STRAVER, PJ
通讯作者：
STRAVER, PJ
影响因子：
1.5
作者：
Larsen, LE;Tjornehoj, K;Uttenthal, Å
通讯作者：
Uttenthal, Å
影响因子：
2.2
作者：
Hagglund, S.;Svensson, C.;Alenius, S.
通讯作者：
Alenius, S.