Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more severe disease in lambs than virus grown in Vero cells.

Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more severe disease in lambs than virus grown in Vero cells.
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DOI:
10.3390/v5112881
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发表时间:
2013-11-22
期刊:
Viruses
影响因子:
--
通讯作者:
Ackermann MR
Ackermann MR
中科院分区:
其他
文献类型:
--
作者:
Derscheid RJ;van Geelen A;McGill JL;Gallup JM;Cihlar T;Sacco RE;Ackermann MR

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呼吸道合胞病毒(RSV)是婴幼儿毛细支气管炎最常见的病因。这些人中有一小部分会患上严重甚至致命的疾病。为了更好地了解严重疾病的发病机制,并开发针对发育不全的婴儿免疫系统的独特疗法,需要婴儿疾病模型。新生羔羊的肺发育和生理学与婴儿相似,绵羊对绵羊、牛或人RSV株易感。与在HEp-2细胞中生长的RSV相比,在Vero(非洲绿色猴)细胞中生长的RSV具有截短的附着G糖蛋白。我们假设在HEp-2细胞中生长的病毒会引起更严重的临床症状和更严重的病理学。为了证实该假设,通过两种不同的递送方法(鼻内和雾化接种)同时用Vero生长或HEp-2生长的RSV孟菲斯37(M37)病毒株接种羔羊,以比较病毒感染和疾病症状。通过鼻内或雾化接种感染HEp-2细胞衍生病毒的羔羊与同样接种Vero生长病毒的羔羊相比,肺部病毒RNA水平显著较高,临床疾病(包括肉眼和组织病理学病变)也更严重。因此,我们的研究结果提供了令人信服的体内证据,证实了以前的体外机制的研究,证明在G糖蛋白表达的差异,RSV生长在Vero细胞中的病毒感染性的差异。
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infant immune system, a model of infant disease is needed. The neonatal lamb pulmonary development and physiology is similar to that of infants, and sheep are susceptible to ovine, bovine, or human strains of RSV. RSV grown in Vero (African green monkey) cells has a truncated attachment G glycoprotein as compared to that grown in HEp-2 cells. We hypothesized that the virus grown in HEp-2 cells would cause more severe clinical symptoms and cause more severe pathology. To confirm the hypothesis, lambs were inoculated simultaneously by two different delivery methods (intranasal and nebulized inoculation) with either Vero-grown or HEp-2-grown RSV Memphis 37 (M37) strain of virus to compare viral infection and disease symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or nebulization inoculation had significantly higher levels of viral RNA in lungs as well as greater clinical disease including both gross and histopathologic lesions compared to lambs similarly inoculated with Vero-grown virus. Thus, our results provide convincing in vivo evidence for differences in viral infectivity that corroborate previous in vitro mechanistic studies demonstrating differences in the G glycoprotein expression by RSV grown in Vero cells.
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