临床基因组研究揭示了登革热病毒基因组高频率突变与登革热病严重程度的关联
Varsha Ravi1,2, Md Imran1, Kriti Khare1,3
1INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Division of Immunology and Infectious Disease Biology, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), North Campus, Near Jubilee Hall, Mall Road, New Delhi, Delhi, 110017, India.
Scientific reports
|May 28, 2025
概括
登革热病毒 (DENV) 突变影响疾病的严重程度. 这项研究将DENV-2基因组突变与临床结果联系起来,确定与轻度,中度和重度登革热相关的关键变异,以便更好地检测和理解.
科学领域:
- 病毒学和分子生物学
- 传染性疾病 传染性疾病
- 公共卫生 公共卫生
背景情况:
- 登革热病毒 (DENV) 构成了全球重大公共卫生挑战,特别是在流行地区.
- 众所周知,像DENV这样的RNA病毒中的遗传突变会影响病毒特征,例如毒性和宿主免疫系统相互作用.
- 了解DENV遗传变异与临床表现之间的关系对于疾病管理至关重要.
研究的目的:
- 在登革热发作期间对DENV突变和相关临床数据进行综合分析.
- 为了确定与不同疾病严重程度 (轻度,中度,严重) 相关的特定DENV遗传变异.
- 通过使用in-silico方法,探索已识别的突变,特别是E蛋白的功能影响.
主要方法:
- 从1310个NS1-抗原阳性登革热患者血清样本中RNA分离.
- 血型鉴定以确定占主导地位的DENV血型,然后使用牛津纳米孔和Illumina平台对DENV-2菌株 (n=1305) 进行全基因组测序.
- 1023个DENV-2基因组的突变分析,覆盖率>50%,包括轻度和重度表型之间的比较分析,以及蛋白模型和对接研究.
主要成果:
- DENV-2是主要的血清型. 在1023个DENV-2基因组中共发现了2667个突变,在严重登革热病例中观察到的突变频率更高.
- 确定了56个显著突变,与轻度,中度和重度登革热相关的特定突变.
- 在DENV E蛋白与DC-SIGN的in-silico对接揭示了与疾病严重程度相关的结合亲和力的差异,这表明严重登革热中非同义突变的功能作用.
结论:
- 已经确定了一组核心的高频率DENV突变,这些突变与明显的登革热病严重程度 (轻度,中度,严重) 有关.
- 在蛋白模型和对接研究强调了严重登革热菌株E蛋白中非同义突变的潜在功能影响.
- 这些发现对于早期检测登革热至关重要,并为DENV病变和疾病进展提供了洞察力.
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