STRUCTURAL AND NONSTRUCTURAL PROTEIN DIVERGENCE CORRELATES WITH STRAIN SPECIFIC VECTOR COMPETENCE FOR ZIKA VIRUS

Background:Zika virus (ZIKV) has become a significant global health threat, with particular attention given to the Asian-lineage strains due to their association with major epidemics and neurological complications. In contrast, African lineages have been less extensively studied, and their transmission dynamics in Neotropical Aedes aegypti remain poorly characterized despite their central role in ZIKV evolutionary history.Methods:We assessed the transmission efficiency of Mexican Ae. aegypti populations orally exposed to blood meals containing either Old-World ZIKV (Dakar) or Neotropical (Honduras) strains. Infection, dissemination, and transmission rates were evaluated, and viral genome copies were quantified in midgut, body, and saliva tissues. Transcriptomic profiling via Illumina sequencing was performed on whole mosquitoes from each treatment group to identify differentially expressed genes (DEGs) and enriched functional pathways.Results:Infection rates were similar between strains, but dissemination and transmission were significantly higher for the Neotropical strain. Viral genome copies were also significantly elevated in all tissues for the Neotropical strain. Whole-genome sequencing identified nonsynonymous substitutions in the Neotropical strain affecting the Envelope (E), NS1, and NS2A proteins, whereas the Old-World isolate harbored a single NS2A substitution. Neotropical ZIKV infection was associated with suppression of immune effectors and peritrophic matrix remodeling genes. Functionally, infection did not alter secondary blood feeding success but imposed significant strain-specific reproductive costs.Conclusions:Mexican Ae. aegypti exhibit markedly higher competence for Neotropical ZIKV, associated with differences in viral replication dynamics and host gene modulation. These findings highlight viral lineage as a key determinant of vector competence, with implications for predicting transmission risk in endemic regions.

研究背景：寨卡病毒（Zika virus, ZIKV）已成为重大全球公共卫生威胁，其中亚洲世系毒株因其与大规模流行及神经系统并发症的关联而受到广泛关注。与之相对，非洲世系毒株的研究尚不够深入，尽管其在寨卡病毒进化历史中扮演核心角色，但它们在新热带区埃及伊蚊（Aedes aegypti）中的传播动力学仍未得到充分阐释。
研究方法：本研究评估了墨西哥埃及伊蚊种群的传播效率，这些蚊虫经口暴露于含旧世界寨卡病毒（达喀尔株）或新热带区毒株（洪都拉斯株）的血餐。研究对感染率、扩散率及传播率进行了检测，并对中肠、蚊体和唾液组织中的病毒基因组拷贝数进行定量分析。此外，通过Illumina测序对各处理组的完整蚊虫开展转录组分析，以筛选差异表达基因（differentially expressed genes, DEGs）并富集功能通路。
研究结果：两种毒株的感染率无显著差异，但新热带区毒株的扩散率与传播率显著更高；新热带区毒株感染的蚊虫所有组织内的病毒基因组拷贝数也显著升高。全基因组测序结果显示，新热带区毒株存在影响包膜蛋白（Envelope, E）、NS1及NS2A蛋白的非同义替换，而旧世界分离株仅携带一处NS2A位点的替换。新热带区寨卡病毒感染与免疫效应因子基因及围食膜基质重塑基因的表达抑制相关。功能层面的实验表明，病毒感染并未改变蚊虫的二次吸血成功率，但带来了显著的毒株特异性生殖成本。
研究结论：墨西哥埃及伊蚊对新热带区寨卡病毒的媒介易感性显著更高，这与病毒复制动力学差异及宿主基因调控模式改变相关。本研究结果凸显病毒世系是决定媒介易感性的关键因素，对预测流行地区的寨卡病毒传播风险具有重要指导意义。