Machmouchi Dana, Courageot Marie-Pierre, El-Kalamouni Chaker, Kohl Alain, Desprès Philippe
Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion, INSERM U1187, CNRS 9192, IRD 249, Plateforme Technologique CYROI, Sainte-Clotilde, La Réunion, France.
UR7506-BioSpect, Université de Reims Champagne-Ardennes, 51100 Reims, France.
PLoS Negl Trop Dis. 2024 Jul 5;18(7):e0012066. doi: 10.1371/journal.pntd.0012066. eCollection 2024 Jul.
Zika virus (ZIKV) has become a global health problem over the past decade due to the extension of the geographic distribution of the Asian/American genotype. Recent epidemics of Asian/American ZIKV have been associated with developmental disorders in humans. There is mounting evidence that African ZIKV may be associated with increased fetal pathogenicity necessitating to pay a greater attention towards currently circulating viral strains in sub-Saharan Africa. Here, we generated an infectious molecular clone GUINEA-18 of a recently transmitted human ZIKV isolate from West Africa, ZIKV-15555. The available infectious molecular clone MR766MC of historical African ZIKV strain MR766-NIID was used for a molecular clone-based comparative study. Viral clones GUINEA-18 and MR766MC were compared for their ability to replicate in VeroE6, A549 and HCM3 cell lines. There was a lower replication rate for GUINEA-18 associated with weaker cytotoxicity and reduced innate immune system activation compared with MR766MC. Analysis of chimeric viruses between viral clones stressed the importance of NS1 to NS4B proteins, with a particular focus of NS4B on GUINEA-18 replicative properties. ZIKV has developed strategies to prevent cytoplasmic stress granule formation which occurs in response to virus infection. GUINEA-18 was greatly efficient in inhibiting stress granule assembly in A549 cells subjected to a physiological stressor, with NS1 to NS4B proteins also being critical in this process. The impact of these GUINEA-18 proteins on viral replicative abilities and host-cell responses to viral infection raises the question of the role of nonstructural proteins in the pathogenicity of currently circulating ZIKV in sub-Saharan Africa.
在过去十年中,由于亚洲/美洲基因型地理分布的扩大,寨卡病毒(ZIKV)已成为一个全球健康问题。最近亚洲/美洲寨卡病毒的流行与人类发育障碍有关。越来越多的证据表明,非洲寨卡病毒可能与胎儿致病性增加有关,因此有必要更加关注撒哈拉以南非洲目前流行的病毒株。在这里,我们构建了一种来自西非的近期传播的人类寨卡病毒分离株ZIKV-15555的感染性分子克隆GUINEA-18。历史上非洲寨卡病毒株MR766-NIID的可用感染性分子克隆MR766MC被用于基于分子克隆的比较研究。比较了病毒克隆GUINEA-18和MR766MC在VeroE6、A549和HCM3细胞系中的复制能力。与MR766MC相比,GUINEA-18的复制率较低,细胞毒性较弱,先天免疫系统激活减少。对病毒克隆之间的嵌合病毒的分析强调了NS1至NS4B蛋白的重要性,特别关注NS4B对GUINEA-18复制特性的影响。寨卡病毒已制定策略来防止因病毒感染而发生的细胞质应激颗粒形成。GUINEA-18在抑制受到生理应激源作用的A549细胞中的应激颗粒组装方面非常有效,NS1至NS4B蛋白在此过程中也至关重要。这些GUINEA-18蛋白对病毒复制能力和宿主细胞对病毒感染反应的影响,引发了关于非结构蛋白在撒哈拉以南非洲目前流行的寨卡病毒致病性中作用的问题。