人工合成的蝙蝠源性腮腺炎病毒的进入、复制、免疫逃逸和神经毒性。

Entry, Replication, Immune Evasion, and Neurotoxicity of Synthetically Engineered Bat-Borne Mumps Virus.

机构信息

Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER), Silver Spring, MD 20993, USA.

出版信息

Cell Rep. 2018 Oct 9;25(2):312-320.e7. doi: 10.1016/j.celrep.2018.09.018.

DOI:10.1016/j.celrep.2018.09.018

PMID:30304672

Abstract

Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of virus isolates. The genome of a virus closely related to human mumps viruses (hMuV) was detected in African fruit bats, batMuV. Efforts to characterize batMuV were based on directed expression of the batMuV glycoproteins or use of recombinant chimeric hMuVs harboring batMuV glycoprotein. Although these studies provided initial insights into the functionality of batMuV glycoproteins, the host range, replication competence, immunomodulatory functions, virulence, and zoonotic potential of batMuV remained elusive. Here, we report the successful rescue of recombinant batMuV. BatMuV infects human cells, is largely resistant to the host interferon response, blocks interferon induction and TNF-α activation, and is neurotoxic in rats. Anti-hMuV antibodies efficiently neutralize batMuV. The striking similarities between hMuV and batMuV point at the putative zoonotic potential of batMuV.

摘要

蝙蝠携带大量具有未知人畜共患潜力的病毒。由于缺乏病毒分离物，对这些病毒进行深入的功能特征分析往往受到阻碍。在非洲果蝠中检测到了一种与人类腮腺炎病毒（hMuV）密切相关的病毒的基因组，即蝙蝠腮腺炎病毒（batMuV）。对 batMuV 进行特征描述的努力是基于对 batMuV 糖蛋白的定向表达或使用携带 batMuV 糖蛋白的重组嵌合 hMuV。尽管这些研究为 batMuV 糖蛋白的功能提供了初步的见解，但 batMuV 的宿主范围、复制能力、免疫调节功能、毒力和人畜共患潜力仍然难以捉摸。在这里，我们报告了重组 batMuV 的成功拯救。BatMuV 感染人类细胞，对宿主干扰素反应具有很强的抗性，可阻断干扰素诱导和 TNF-α 的激活，并在大鼠中具有神经毒性。抗 hMuV 抗体可有效中和 batMuV。hMuV 和 batMuV 之间的惊人相似之处表明 batMuV 具有潜在的人畜共患潜力。