Cell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência (IGC), 2780-156 Oeiras, Portugal.
Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.
J Cell Sci. 2017 Dec 1;130(23):4038-4050. doi: 10.1242/jcs.210807. Epub 2017 Oct 23.
Influenza A is a rapidly evolving virus that is successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite genome of RNA (in the form of viral ribonucleoproteins, vRNPs), and viral genome assembly - with its implications to public health - is not completely understood. It has previously been reported that vRNPs are transported to the cell surface on Rab11-containing vesicles by using microtubules but, so far, no molecular motor has been assigned to the process. Here, we have identified KIF13A, a member of the kinesin-3 family, as the first molecular motor to efficiently transport vRNP-Rab11 vesicles during infection with influenza A. Depletion of KIF13A resulted in reduced viral titers and less accumulation of vRNPs at the cell surface, without interfering with the levels of other viral proteins at sites of viral assembly. In addition, when overexpressed and following two separate approaches to displace vRNP-Rab11 vesicles, KIF13A increased levels of vRNP at the plasma membrane. Together, our results show that KIF13A plays an important role in the transport of influenza A vRNPs, a crucial step for viral assembly.This article has an associated First Person interview with the first author of the paper.
甲型流感病毒是一种快速进化的病毒，能够在人类中引发周期性的流行和偶尔的大流行。病毒的组装过程非常复杂，因为它包含一个由 8 个部分组成的 RNA 基因组（以病毒核糖核蛋白的形式存在），而病毒基因组的组装及其对公共卫生的影响尚未完全了解。此前有报道称，vRNPs 通过含有 Rab11 的小泡在微管上被运送到细胞表面，但到目前为止，还没有分子马达被分配到这个过程中。在这里，我们鉴定出 KIF13A 是驱动蛋白-3 家族的一个成员，是在甲型流感病毒感染过程中有效运输 vRNP-Rab11 小泡的第一个分子马达。KIF13A 的耗竭导致病毒滴度降低，vRNPs 在细胞表面的积累减少，而不干扰病毒组装部位其他病毒蛋白的水平。此外，当过量表达并通过两种不同的方法置换 vRNP-Rab11 小泡时，KIF13A 增加了质膜上 vRNP 的水平。总之，我们的研究结果表明，KIF13A 在甲型流感病毒 vRNPs 的运输中发挥着重要作用，这是病毒组装的关键步骤。本文有一篇与论文第一作者的相关第一人称采访。
