WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
J Virol. 2018 Jan 30;92(4). doi: 10.1128/JVI.01322-17. Print 2018 Feb 15.
Small-animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Among those described to date, infections in cotton rats, mice, guinea pigs, chinchillas, and Syrian hamsters with hRSV strains Long and/or A2 have been well characterized, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection, but the pathogenesis and immune responses elicited following infection have not been well characterized. Here, we describe the infection of adult ferrets with hRSV Long or A2 via the intranasal route and characterized virus replication, as well as cytokine induction, in the upper and lower airways. Virus replication and cytokine induction during the acute phase of infection (days 0 to 15 postinfection) were similar between the two strains, and both elicited high levels of F glycoprotein-specific binding and neutralizing antibodies following virus clearance (days 16 to 22 postinfection). Importantly, we demonstrate transmission from experimentally infected donor ferrets to cohoused naive recipients and have characterized virus replication and cytokine induction in the upper airways of infected contact animals. Together, these studies provide a direct comparison of the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of this animal model to study serological responses and examine interventions that limit transmission of hRSV. Ferrets have been widely used to study pathogenesis, immunity, and transmission following human influenza virus infections; however, far less is known regarding the utility of the ferret model to study hRSV infections. Following intranasal infection of adult ferrets with the well-characterized Long or A2 strain of hRSV, we report virus replication and cytokine induction in the upper and lower airways, as well as the development of virus-specific humoral responses. Importantly, we demonstrate transmission of hRSV from experimentally infected donor ferrets to cohoused naive recipients. Together, these findings significantly enhance our understanding of the utility of the ferret as a small-animal model to investigate aspects of hRSV pathogenesis and immunity.
小动物模型已被用于获得有关人类呼吸道合胞病毒（hRSV）感染后发病机制和免疫反应的许多见解。迄今为止，已对棉鼠、小鼠、豚鼠、龙猫和叙利亚仓鼠中感染 hRSV Long 和/或 A2 株的感染进行了很好的描述，尽管也检查了临床分离株。雪貂也易感染 hRSV，但感染后引发的发病机制和免疫反应尚未得到很好的描述。在这里，我们通过鼻腔途径描述了成年雪貂感染 hRSV Long 或 A2，并描述了病毒在上、下呼吸道中的复制以及细胞因子的诱导。两种菌株在感染的急性期（感染后 0 至 15 天）的病毒复制和细胞因子诱导相似，并且在病毒清除后（感染后 16 至 22 天）都产生了高水平的 F 糖蛋白特异性结合和中和抗体。重要的是，我们证明了来自实验感染供体雪貂的病毒传播给同居的未感染受体，并描述了感染接触动物上呼吸道中的病毒复制和细胞因子诱导。这些研究共同提供了 hRSV Long 和 A2 在雪貂中的发病机制的直接比较，并强调了该动物模型研究血清学反应和检查限制 hRSV 传播的干预措施的潜力。雪貂已被广泛用于研究人类流感病毒感染后的发病机制、免疫和传播；然而，对于该模型用于研究 hRSV 感染的效用知之甚少。通过鼻腔感染成年雪貂，用特征明确的 Long 或 A2 株 hRSV，我们报告了上、下呼吸道中的病毒复制和细胞因子诱导，以及病毒特异性体液反应的发展。重要的是，我们证明了 hRSV 从实验感染的供体雪貂传播到同居的未感染受体。这些发现共同显著提高了我们对雪貂作为小动物模型用于研究 hRSV 发病机制和免疫的用途的理解。
