Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSVA11EGFP(5)]. A recombinant laboratory-adapted HRSV strain [rHRSVA2EGFP(5)] was used as a direct comparison. Our results show that rHRSVA11EGFP(5) replicated to higher viral titres than laboratory-adapted rHRSVA2EGFP(5) in the URT of cotton rats and mice. HRSV-infected cells were detected as early as 2 days post-inoculation in both species in the nasal septa and lungs. Infection was predominantly present in ciliated epithelial cells in cotton rats and in the olfactory mucosa of mice. In our opinion, this study highlights that the choice of virus strain is important when studying HRSV pathogenesis in vivo and demonstrates that A11 is a representative clinical-based virus. Additionally, we show critical differences in tropism and inflammation when comparing HRSV infection of cotton rats and mice.

中文翻译：

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实验室适应和基于临床分离物的重组人呼吸道合胞病毒的体内比较。

人呼吸道合胞病毒（HRSV）是婴儿严重呼吸道疾病的主要原因。大多数HRSV感染仍然局限于上呼吸道（URT），但是在少数患者中，感染会扩散到下呼吸道，导致细支气管炎或肺炎。我们对HRSV的发病机理以及哪些因素决定疾病的严重程度了解有限，部分原因是适应组织培养的病毒的广泛使用。在这里，我们研究了棉鼠，BALB / cJ小鼠和C57BL / 6小鼠中HRSV的早期病毒传播和向性。我们使用了一种基于表达EGFP [rHRSV A11 EGFP（5）]的A亚群临床分离株（A11）的新型重组（r）菌株。重组实验室适应性HRSV菌株[rHRSV A2EGFP（5）]被用作直接比较。我们的结果表明，在棉花大鼠和小鼠的URT中，rHRSV A11 EGFP（5）复制的病毒滴度比实验室适应的rHRSV A2 EGFP（5）高。最早在接种后两天，在鼻中隔和肺部的两种物种中都检测到了HRSV感染的细胞。感染主要存在于棉花大鼠的纤毛上皮细胞和小鼠的嗅觉粘膜中。我们认为，这项研究强调在体内研究HRSV发病机理时病毒株的选择很重要，并证明A11是一种典型的基于临床的病毒。此外，当比较棉鼠和小鼠的HRSV感染时，我们在嗜性和炎症方面显示出关键差异。