Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Sci Rep. 2018 Oct 30;8(1):15994. doi: 10.1038/s41598-018-34484-7.
Continued outbreaks of Henipaviruses in South Asia and Australia cause severe and lethal disease in both humans and animals. Together, with evidence of human to human transmission for Nipah virus and the lack of preventative or therapeutic measures, its threat to cause a widespread outbreak and its potential for weaponization has increased. In this study we demonstrate how overexpression of the Nipah virus nucleocapsid protein regulates viral polymerase activity and viral RNA production. By overexpressing the Nipah virus nucleocapsid protein in trans viral transcription was inhibited; however, an increase in viral genome synthesis was observed. Together, the bias of polymerase activity towards genome production led to the severe inhibition of viral progeny. We identified two domains within the nucleocapsid protein, which were each independently capable of binding the viral phosphoprotein. Evident by our data, we propose that the nucleocapsid protein's ability to interact with the phosphoprotein of the polymerase complex causes a change in polymerase activity and subsequent deficiency in viral replication. This study not only provides insights into the dynamics of Henipavirus RNA synthesis and replication, but also provides insight into potential targets for antiviral drug development.
在南亚和澳大利亚，亨尼帕病毒的持续爆发导致人类和动物患上严重且致命的疾病。尼帕病毒已被证实存在人际传播，且目前尚无预防或治疗措施，因此其爆发和潜在的武器化风险增加了。在这项研究中，我们展示了尼帕病毒核衣壳蛋白的过表达如何调节病毒聚合酶活性和病毒 RNA 产生。通过转病毒转录过表达尼帕病毒核衣壳蛋白，病毒转录被抑制；然而，观察到病毒基因组合成增加。聚合酶活性偏向基因组产生的这种偏倚导致病毒后代的严重抑制。我们确定了核衣壳蛋白内的两个结构域，它们各自都能够独立地与病毒磷蛋白结合。根据我们的数据，我们提出核衣壳蛋白与聚合酶复合物的磷蛋白相互作用的能力导致聚合酶活性的改变，随后导致病毒复制缺陷。这项研究不仅提供了对亨尼帕病毒 RNA 合成和复制动态的深入了解，还为抗病毒药物开发提供了潜在的靶点。
