Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):804-9. doi: 10.1073/pnas.1013155108. Epub 2010 Dec 27.
The Bunyaviridae family includes pathogens of medical and veterinary importance. Rift Valley fever virus (RVFV), a member in the Phlebovirus genus of the family Bunyaviridae, is endemic to sub-Saharan Africa and causes a mosquito-borne disease in ruminants and humans. Viruses in the family Bunyaviridae carry a tripartite, single-stranded, negative-sense RNA genome composed of L, M, and S RNAs. Little is known about how the three genomic RNA segments are copackaged to generate infectious bunyaviruses. We explored the mechanism that governs the copackaging of the three genomic RNAs into RVFV particles. The expression of viral structural proteins along with replicating S and M RNAs resulted in the copackaging of both RNAs into RVFV-like particles, while replacing M RNA with M1 RNA, lacking a part of the M RNA 5' UTR, abrogated the RNA copackaging. L RNA was efficiently packaged into virus particles released from cells supporting the replication of L, M, and S RNAs, and replacing M RNA with M1 RNA abolished the packaging of L RNA. Detailed analyses using various combinations of replicating viral RNAs suggest that M RNA alone or a coordinated function of M and S RNAs exerted efficient L RNA packaging either directly or indirectly. Collectively, these data are consistent with the possibility that specific intermolecular interactions among the three viral RNAs drive the copackaging of these RNAs to produce infectious RVFV.
布尼亚病毒科包括具有医学和兽医重要性的病原体。裂谷热病毒 (RVFV) 是布尼亚病毒科菲洛病毒属的成员，流行于撒哈拉以南非洲地区，可引起反刍动物和人类的蚊媒疾病。布尼亚病毒科的病毒携带一个由 L、M 和 S RNA 组成的三分体、单链、负义 RNA 基因组。人们对三个基因组 RNA 片段如何被共同包装以产生感染性布尼亚病毒知之甚少。我们探索了控制三种基因组 RNA 共同包装到 RVFV 颗粒中的机制。病毒结构蛋白的表达以及复制的 S 和 M RNA 导致这两种 RNA 共同包装到 RVFV 样颗粒中，而用缺乏 M RNA 5'UTR 一部分的 M1 RNA 替换 M RNA 则会破坏 RNA 共同包装。L RNA 被有效地包装到从支持 L、M 和 S RNA 复制的细胞中释放的病毒颗粒中，而用 M1 RNA 替换 M RNA 则会阻止 L RNA 的包装。使用复制病毒 RNA 的各种组合进行的详细分析表明，M RNA 单独或 M 和 S RNA 的协调功能直接或间接地发挥了有效包装 L RNA 的作用。总的来说，这些数据表明，三种病毒 RNA 之间的特定分子间相互作用可能驱动这些 RNA 的共同包装，从而产生感染性 RVFV。
