A bioinformatics approach toward understanding interplay betweenchronic virus infections and human antiviral immune responses

理解慢性病毒感染与人类抗病毒免疫反应之间相互作用的生物信息学方法

• 批准号: 23659232
• 负责人: UENO Takamasa
• 金额: $ 2.58万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659232/
• 关键词: 感染防御; ワクチン; ウイルス; 感染症; 進化; ＨＩＶ; 免疫回避; 感染防御; ワクチン; ウイルス; 感染症; 進化; ＨＩＶ; 免疫回避

HIV -1 Nef is required for efficient viral replication and pathogenesis. However , the extent to which Nef ’ s functions are maintained in natural sequences duringchronic infection, and their clinical relevance, remains incompletely characterized. Relativeto a control Nef from HIV -1 strain SF2, HLA class I and CD4 down-regulation activities of46 plasma RNA Nef sequences derived from unique chronic infected individuals weregenerally high and displayed narrow dynamic ranges, whereas Nef-mediated virioninfectivity , PBMC replication and CD74 up-regulation exhibited broader dynamic ranges.80% of patient-derived Nefs were active for at least three functions examined. Functionalco-dependencies were identified, including positive correlations between CD4down-regulation and virion infectivity , replication, and CD74 up-regulation, and betweenCD74 up-regulation and PBMC replication. Nef-mediated virion infectivity inverselycorrelated with patient CD4+ T -cell count. Strong functional co-dependencies and thepolyfunctional nature of patient-derived Nef sequences suggest a phenotypic requirementto maintain multiple Nef functions during chronic infection

HIV -1 NEF是有效的病毒复制和发病机理所必需的。但是，在慢性感染期间，NEF功能保持在自然序列以及其临床相关性的程度尚未完全表征。 Relativeto a control Nef from HIV -1 strain SF2, HLA class I and CD4 down-regulation activities of 46 plasma RNA Nef sequences derived from unique chronic infected individuals were generally high and displayed narrow dynamic ranges, whereas Nef-mediated virioninfectivity, PBMC replication and CD74 up-regulation exposed broader dynamic ranges.80% of patient-derived Nefs were至少检查了三个功能。鉴定了功能性依赖性，包括CD4Down调节与病毒体感染，复制和CD74上调之间的正相关，以及CD74上调和PBMC复制之间的正相关。 NEF介导的病毒体感染与患者CD4+ T细胞计数不相同。强大的功能共同依赖性和患者衍生的NEF序列的功能性性质提出了在慢性感染过程中维持多个NEF功能的表型要求