Inhibition of replication of the human cytomegalovirus through interaction with tropism-relevant envelope protein

通过与趋向性相关包膜蛋白相互作用抑制人巨细胞病毒的复制

• 批准号: 230446674
• 负责人: Professor Dr. Christian Sinzger
• 金额: --
• 依托单位: Institut für Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230446674?language=en
• 关键词: Inhibition; replication; human; cytomegalovirus; through

About 50 % of the population is infected with the human cytomegalovirus (HCMV). Following infection the virus establishes lifelong persistence in the organism without clinical symptoms. Immunosuppression can lead to reactivation, hematogenous dissemination and eventually organ manifestation of the virus with severe morbidity particularly in lung and gastrointestinal tract. The infection of vascular endothelial cells (ECs) and blood cells depends mainly on the viral genes UL128, UL130 and UL131A. We have recently mapped these genes by a systematic mutational approach with regard to functionally important charged peptide clusters. Based on this information we now aim at (i) revealing the molecular mechanisms underlying EC infection, (ii) development of candidate vaccine strains that are attenuated regarding EC infection and (iii) targeted development of inhibitory peptides with the potential to prevent hematogenous dissemination of HCMV. First we will analyze how the various mutations affect the protein composition of the viral envelope, virion attachment to ECs and fusion of viral envelope with cellular membranes. Mutations that reduce EC tropism but maintain the protein composition of the virus envelope will be combined for vaccine development. Peptides with impact on the interaction within the UL128-131A containing envelope protein complex will be further evaluated regarding suitability as potential antiviral drugs.

约50%的人口感染了人巨细胞病毒（HCMV）。感染后，病毒在生物体中建立终身持久性，无临床症状。免疫抑制可导致病毒的再激活、血行播散和最终器官表现，尤其是肺和胃肠道的严重发病率。病毒对血管内皮细胞和血细胞的感染主要依赖于病毒基因UL 128、UL 130和UL 131 A。我们最近绘制了这些基因的系统突变的方法方面的功能重要的带电肽簇。基于这些信息，我们现在的目标是（i）揭示EC感染的分子机制，（ii）开发针对EC感染减毒的候选疫苗株，以及（iii）靶向开发具有预防HCMV血行播散潜力的抑制肽。 首先，我们将分析各种突变如何影响病毒包膜的蛋白质组成，病毒粒子附着到EC和病毒包膜与细胞膜的融合。降低EC嗜性但保持病毒包膜蛋白组成的突变将组合用于疫苗开发。将进一步评价对含UL 128 - 131 A包膜蛋白复合物内相互作用有影响的肽作为潜在抗病毒药物的适用性。