叙利亚仓鼠(Mesocricetus auratus)作为呼吸道合胞病毒感染的上呼吸道模型

Sophie M Kolbe, Kate Guilfoyle, Wencke Reineking, Geert van Amerongen, Guido van der Net, Sandra Lockow, Wolfgang Baumgärtner, Martin Ludlow, Albert D M E Osterhaus
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摘要

呼吸道合胞病毒(RSV)是儿童、免疫功能低下者和老年人呼吸道感染的主要原因之一。最近已批准用于成人的疫苗,尽管正在进一步努力开发适合儿童的干预措施,但呼吸道合胞病毒感染的动物模型有限。可采用棉花大鼠和雪貂模型进行预防和治疗性治疗的临床前疗效试验。然而,这些方法可能很昂贵,难以获得来源和饲养,并且通常具有局限性,例如病毒在呼吸道中的复制不足和/或缺乏水平传播。本研究将一株表达EGFP的重组RSV-A-0594菌株经鼻接种给价格相对低廉、易于获取和饲养的叙利亚仓鼠(Mesocricetus auratus),并进行病毒学和病理学分析。评估病毒复制并与雪貂模型中的病毒复制进行比较。虽然叙利亚仓鼠下呼吸道的病毒感染有限,但我们发现当代重组RSV-A菌株在叙利亚仓鼠上呼吸道有效复制(滴度高达4.5 Log10 TCID50/g和12 Log10 RNA拷贝/g)。这些滴度与感染同一病毒株后雪貂上呼吸道组织中的滴度相当(高达6.0 Log10 TCID50/g和12 Log10 RNA拷贝/g)。在紫外光下,鼻鼻甲可见指示病毒感染的荧光区,组织学检查显示该组织粘膜炎症伴坏死细胞。综上所述,与雪貂相比,叙利亚仓鼠通常表现出较轻的全身和肺部变化,但似乎确实是上呼吸道感染RSV的有希望的模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Syrian hamsters (Mesocricetus auratus) as an upper respiratory tract model for respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is one of the leading causes of respiratory tract infection in children, immunocompromised individuals and older adults. Vaccines have recently been approved for use in adults and although further efforts to develop suitable interventions for children are ongoing, there are limited animal models for RSV infection. For preclinical efficacy testing of prophylactic and therapeutic treatments cotton rat and ferret models can be used. However, these can be expensive, difficult to source and house, and often have limitations such as insufficient virus replication in the respiratory tract and/or lack of horizontal transmission. In this study, Syrian hamsters (Mesocricetus auratus), which are relatively cheap, easy to source and house, were inoculated intranasally with a recombinant RSV-A-0594 strain expressing EGFP and using virological and pathological analyses. Viral replication was assessed and compared to viral replication in the ferret model. Although there was limited virus infection of the lower respiratory tract of Syrian hamsters, we show that a contemporary recombinant RSV-A strain replicates efficiently in the upper respiratory tract of Syrian hamsters (titers up to 4.5 Log10 TCID50/g and 12 Log10 RNA copies/g). These titers are comparable to those found in the ferret upper respiratory tract tissues post-infection with the same virus strain (up to 6.0 Log10 TCID50/g and 12 Log 10 RNA copies/g). Fluorescent regions indicating virus infection were macroscopically visible under UV-light in the nasal turbinates and histological assessment showed mucosal inflammation with necrotic cells in this tissue. In summary, Syrian hamsters generally displayed less severe systemic and pulmonary changes than ferrets, but do appear to be a promising model for upper respiratory tract infection with RSV.

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