Krüger Nadine, Sauder Christian, Hoffmann Markus, Örvell Claes, Drexler Jan Felix, Rubin Steven, Herrler Georg
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER), Silver Spring, MD, USA.
J Gen Virol. 2016 Nov;97(11):2837-2848. doi: 10.1099/jgv.0.000596. Epub 2016 Sep 2.
A recent study reported the detection of a bat-derived virus (BatPV/Epo_spe/AR1/DCR/2009, batMuV) with phylogenetic relatedness to human mumps virus (hMuV). Since all efforts to isolate infectious batMuV have reportedly failed, we generated recombinant mumps viruses (rMuVs) in which the open reading frames (ORFs) of the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins of an hMuV strain were replaced by the corresponding ORFs of batMuV. The batMuV F and HN proteins were successfully incorporated into viral particles and the resultant chimeric virus was able to mediate infection of Vero cells. Distinct differences were observed between the fusogenicity of rMuVs expressing one or both batMuV glycoproteins: viruses expressing batMuV F were highly fusogenic, regardless of the origin of HN. In contrast, rMuVs expressing human F and bat-derived HN proteins were less fusogenic compared to hMuV. The growth kinetics of chimeric MuVs expressing batMuV HN in combination with either hMuV or batMuV F were similar to that of the backbone virus, whereas a delay in virus replication was obtained for rMuVs harbouring batMuV F and hMuV HN. Replacement of the hMuV F and HN genes or the HN gene alone by the corresponding batMuV genes led to a slight reduction in neurovirulence of the highly neurovirulent backbone strain. Neutralizing antibodies inhibited infection mediated by all recombinant viruses generated. Furthermore, group IV anti-MuV antibodies inhibited the neuraminidase activity of bat-derived HN. Our study reports the successful generation of chimeric MuVs expressing the F and HN proteins of batMuV, providing a means for further examination of this novel batMuV.
最近的一项研究报告称，检测到一种与人类腮腺炎病毒（hMuV）具有系统发育相关性的蝙蝠源病毒（BatPV/Epo_spe/AR1/DCR/2009，蝙蝠腮腺炎病毒）。据报道，由于所有分离传染性蝙蝠腮腺炎病毒的努力均告失败，我们构建了重组腮腺炎病毒（rMuV），其中一株hMuV毒株的融合（F）蛋白和血凝素神经氨酸酶（HN）糖蛋白的开放阅读框（ORF）被蝙蝠腮腺炎病毒的相应ORF所取代。蝙蝠腮腺炎病毒F和HN蛋白成功整合到病毒颗粒中，所得嵌合病毒能够介导对Vero细胞的感染。在表达一种或两种蝙蝠腮腺炎病毒糖蛋白的rMuV的融合活性之间观察到明显差异：表达蝙蝠腮腺炎病毒F的病毒具有高度融合活性，而与HN的来源无关。相比之下，表达人类F和蝙蝠源HN蛋白的rMuV与hMuV相比融合活性较低。表达蝙蝠腮腺炎病毒HN与hMuV或蝙蝠腮腺炎病毒F组合的嵌合腮腺炎病毒的生长动力学与主干病毒相似，而含有蝙蝠腮腺炎病毒F和hMuV HN的rMuV在病毒复制方面出现延迟。用相应的蝙蝠腮腺炎病毒基因替换hMuV的F和HN基因或仅替换HN基因，导致高神经毒性主干毒株的神经毒性略有降低。中和抗体抑制了所有产生的重组病毒介导的感染。此外，IV组抗腮腺炎病毒抗体抑制了蝙蝠源HN的神经氨酸酶活性。我们的研究报告了成功构建表达蝙蝠腮腺炎病毒F和HN蛋白的嵌合腮腺炎病毒，为进一步研究这种新型蝙蝠腮腺炎病毒提供了一种手段。
