对人类PLVAP基因结构和功能的非同义SNP影响的计算分析
Mehnaj Khatoon1, Yamini Sri Sekar1, Swati Rani1
1ICAR- National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, 560 064, Karnataka, India.
Journal of applied genetics
|December 22, 2025
概括
研究血囊泡相关蛋白 (PLVAP) 基因变异的研究揭示了日本脑炎病毒 (JEV) 如何进入大脑. 特定的突变影响病毒的进入,为诊断和抗病毒疗法提供了洞察力.
科学领域:
- 基因组学和生物信息学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 血囊相关蛋白 (PLVAP) 对于血脑屏障 (BBB) 完整性至关重要,并作为日本脑炎病毒 (JEV) 的受体.
- 了解PLVAP的遗传变异如何影响JEV神经侵入对于疾病预防和治疗至关重要.
研究的目的:
- 通过计算分析PLVAP基因中非同义单核酸多态 (nsSNP) 对JEV宿主相互作用的功能影响.
- 确定影响JEV结合和进入中枢神经系统的特定PLVAP变异.
主要方法:
- 从NCBI dbSNP中检索和分析了11,883个SNP,确定了403个独特的nsSNP.
- 进行了蛋白质稳定性,乱,保存和分子对接分析,以评估变体的影响.
- 根据其预测的影响,优先考虑了五个关键的nsSNP (R26H,I35T,E175G,V44G,I39S).
主要成果:
- 确定了43个严重破坏PLVAP结构的nsSNP和29个有害的nsSNP.
- 五种关键变异显示出明显的破坏稳定作用和改变了PLVAP-JEV结合相互作用.
- 预计突变会改变JEV的进入效率和宿主易感性.
结论:
- PLVAP变种可以影响JEV神经侵入,表明它们作为风险分层的生物标志物的潜力.
- 这些发现支持针对PLVAP-JEV相互作用的治疗策略,用于抗病毒药物发现.
- 计算方法可以扩展到其他flavivirus与宿主相互作用,用于个性化医学.
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