Replication is the key barrier during the dual-host adaptation of mosquito-borne flaviviruses.

Replication is the key barrier during the dual-host adaptation of mosquito-borne flaviviruses.
复制标题

复制是蚊媒黄病毒双宿主适应过程中的关键障碍

DOI:
10.1073/pnas.2110491119
复制
发表时间:
2022-03-22
影响因子:
11.1
通讯作者:
Zheng A
Zheng A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang Y;Liang D;Yuan F;Yan Y;Wang Z;Liu P;Yu Q;Zhang X;Wang X;Zheng A

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大多数病毒的宿主范围相对较窄。相比之下,媒介传播的黄病毒,如登革热病毒和寨卡病毒,保持其在节肢动物和脊椎动物之间的传播周期,属于不同的门。这些病毒如何适应两个门的不同细胞环境?通过比较单宿主昆虫特异性黄病毒和双宿主寨卡病毒,我们确定了决定MBF宿主向性的三个关键分子因素。这项研究将大大增加对蚊媒黄病毒进入、复制和跨物种进化的理解。蚊传黄病毒(MBF)适应于蚊和脊椎动物之间的双宿主传播循环。双宿主附属昆虫特异性黄病毒(dISF),从蚊子中发现,在遗传学上与MBF相似,但不感染脊椎动物。因此,dISF-MBF嵌合体是研究MBF双宿主适应性的理想模型。使用假感染性报告病毒颗粒和反向遗传学系统,我们发现dISFs进入脊椎动物细胞的MBFs一样有效,但未能启动复制。东港病毒(DONV)(一种dISF)的非翻译区(UTR)与寨卡病毒(ZIKV)的非翻译区(UTR)的交换挽救了脊椎动物细胞中的DONV复制,并进一步绘制了关键的二级RNA结构。针对脊椎动物细胞中的ZIKV复制筛选必需的UTR结合宿主因子,其显示不同的结合模式。因此,我们的数据表明,进入后的跨物种传播机制的MBFs,而UTR-主机的相互作用是至关重要的双主机适应。
Most viruses have a relatively narrow host range. In contrast, vector-borne flaviviruses, such as dengue virus and Zika virus, maintain their transmission cycle between arthropods and vertebrates, belonging to different phyla. How do these viruses adapt to the distinct cellular environments of two phyla? By comparing the single-host insect--specific flavivirus and dual-host Zika virus, we identified three key molecular factors that determine MBF host tropism. This study will greatly increase the understanding of entry, replication, and cross-species evolution of mosquito-borne flaviviruses. Mosquito-borne flaviviruses (MBFs) adapt to a dual-host transmission circle between mosquitoes and vertebrates. Dual-host affiliated insect-specific flaviviruses (dISFs), discovered from mosquitoes, are phylogenetically similar to MBFs but do not infect vertebrates. Thus, dISF–MBF chimeras could be an ideal model to study the dual-host adaptation of MBFs. Using the pseudoinfectious reporter virus particle and reverse genetics systems, we found dISFs entered vertebrate cells as efficiently as the MBFs but failed to initiate replication. Exchange of the untranslational regions (UTRs) of Donggang virus (DONV), a dISF, with those from Zika virus (ZIKV) rescued DONV replication in vertebrate cells, and critical secondary RNA structures were further mapped. Essential UTR-binding host factors were screened for ZIKV replication in vertebrate cells, displaying different binding patterns. Therefore, our data demonstrate a post-entry cross-species transmission mechanism of MBFs, while UTR-host interaction is critical for dual-host adaptation.
电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
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