Branigan Patrick J, Liu Changbao, Day Nicole D, Gutshall Lester L, Sarisky Robert T, Del Vecchio Alfred M
Infectious Diseases Research, Centocor, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA.
Virol J. 2005 Jul 13;2:54. doi: 10.1186/1743-422X-2-54.
Human respiratory syncytial virus (HRSV) is an important respiratory pathogen primarily affecting infants, young children, transplant recipients and the elderly. The F protein is the only virion envelope protein necessary and sufficient for virus replication and fusion of the viral envelope membrane with the target host cell. During natural infection, HRSV replication is limited to respiratory epithelial cells with disseminated infection rarely, if ever, occurring even in immunocompromised patients. However, in vitro infection of multiple human and non-human cell types other than those of pulmonary tract origin has been reported. To better define host cell surface molecules that mediate viral entry and dissect the factors controlling permissivity for HRSV, we explored the host range of HRSV F protein mediated fusion. Using a novel recombinant reporter gene based fusion assay, HRSV F protein was shown to mediate fusion with cells derived from a wide range of vertebrate species including human, feline, equine, canine, bat, rodent, avian, porcine and even amphibian (Xenopus). That finding was extended using a recombinant HRSV engineered to express green fluorescent protein (GFP), to confirm that viral mRNA expression is limited in several cell types. These findings suggest that HRSV F protein interacts with either highly conserved host cell surface molecules or can use multiple mechanisms to enter cells, and that the primary determinants of HRSV host range are at steps post-entry.
人呼吸道合胞病毒（HRSV）是一种重要的呼吸道病原体，主要影响婴儿、幼儿、移植受者和老年人。F蛋白是病毒复制以及病毒包膜与靶宿主细胞融合所必需且足够的唯一病毒体包膜蛋白。在自然感染期间，HRSV复制局限于呼吸道上皮细胞，即使在免疫功能低下的患者中也极少发生播散性感染。然而，已有报道称HRSV可在体外感染多种非肺源性的人类和非人类细胞类型。为了更好地确定介导病毒进入的宿主细胞表面分子，并剖析控制HRSV易感性的因素，我们探究了HRSV F蛋白介导的融合的宿主范围。使用一种基于新型重组报告基因的融合测定法，结果显示HRSV F蛋白可介导与多种脊椎动物来源的细胞发生融合，这些动物包括人类、猫、马、犬、蝙蝠、啮齿动物、鸟类、猪甚至两栖动物（非洲爪蟾）。利用一种经基因工程改造以表达绿色荧光蛋白（GFP）的重组HRSV扩展了该发现，以证实病毒mRNA表达在几种细胞类型中受到限制。这些发现表明，HRSV F蛋白与高度保守的宿主细胞表面分子相互作用，或者可以利用多种机制进入细胞，并且HRSV宿主范围的主要决定因素在于进入后的步骤。
