影响2型登革热病毒复制和病原性的遗传区域
Yoshihiro Samune1, Akatsuki Saito2, Tadahiro Sasaki1
1Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
PLoS neglected tropical diseases
|January 8, 2024
概括
登革热病毒 (DENV) 基因型表现出不同的复制和严重程度. 全球DENV2基因型结构和NS1-NS2B蛋白质在小鼠中增强病毒复制和致病性,这表明序列差异驱动了这些变异.
科学领域:
- 病毒学 病毒学
- 传染性疾病 传染性疾病
- 分子生物学分子生物学
背景情况:
- 登革热病毒 (DENV) 是一个重要的全球健康威胁,在泰国等特有地区传播的四种血清型.
- 在泰国进行的DENV2基因型测序显示,亚洲I和新兴的Cosmopolitan基因型的共同循环.
- DENV2基因型差异对病毒复制和致病性的影响尚不清楚.
研究的目的:
- 调查不同的DENV2基因型 (亚洲-I和宇宙) 是否表现出不同的病毒复制能力和致病性.
- 确定负责DENV2感染性和疾病严重程度观察到的差异的特定病毒成分.
主要方法:
- 使用循环聚合酶延伸反应生成的亲属和仿真DENV2病毒,在亚洲I型和世界型基因型之间交换基因.
- 使用聚焦形成试验 (FFA),单回合传染粒子试验和复制子试验评估病毒复制和传染性.
- 评估了干扰素受体淘汰小鼠的致病性,以确定体内病毒标位和疾病过程.
主要成果:
- 具有宇宙基因型结构蛋白 (特别是prM/E) 和NS1-NS2B蛋白质的化学病毒显示出更大的焦点大小,更高的感染标位和增加的记者基因表达.
- 在测试中,宇宙 DENV2 结构和 NS1-NS2B 蛋白质显著增强了病毒复制和光酶活性.
- 在小鼠中,包含Cosmopolitan结构和NS1-NS2B蛋白质的病毒表现出更高的血位和更严重的疾病进展.
结论:
- 在DENV2的结构蛋白和NS1-NS2B区域内的序列变异有助于病毒复制,感染性和致病性的差异.
- 与亚洲-I基因型相比,DENV2的Cosmopolitan基因型可能具有增强的复制和疾病诱导特性.
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