Studies on Molecular Mechanisms of Host-Pathogen Interactions of Nidoviruses of Veterinary Importance

兽医重要巢状病毒宿主-病原体相互作用的分子机制研究

• 批准号: RGPIN-2017-04897
• 负责人: Abrahamyan, Levon
• 金额: $ 1.82万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=643383
• 关键词: Studies; Molecular; Mechanisms; Host; Pathogen

The porcine reproductive and*respiratory syndrome virus (PRRSV) and the porcine epidemic diarrhea virus*(PEDV) are responsible for severe agricultural economic losses and are*considered to be the primary emerging livestock pathogens in Canada and worldwide.*Both viruses are single-stranded, positive-sense RNA, enveloped porcine*nidoviruses and share common characteristics including similar particle*structure, conserved genomic organization and replication strategy. The*traditional approach to develop vaccines has not resulted in reliable and*effective vaccines, and these viruses remain a major threat to the swine*industry worldwide.***We believe that insufficient*understanding of nidovirus-host interactions hinders the development of*effective vaccines against nidoviruses. Therefore, we propose to investigate the molecular mechanisms of animal*nidovirus-host interactions in order to identify novel antiviral targets and*develop effective prevention strategies.***The*long-term goal of this program is to gain a better understanding of the molecular*mechanisms of interactions between animal nidoviruses and their hosts in order*to develop new strategies for effective control of viral infections. The short-term*goal for the next five years is to elucidate PRRSV and PEDV interactions with*host cells by focusing on the characterization and comparison of early events*in nidovirus infection. To address this objective, we will: 1) investigate the*cellular and molecular mechanisms underlying porcine nidovirus entry into host*cells, and 2) analyze proteomic profiles of host cell responses to viral*infection, characterize the composition of nidoviruses, and identify the host*proteins associated with the viral particle. The accomplishment of these*specific objectives will lead to an understanding of the nature of the*virus-host interaction during the earliest stage of nidovirus infection. We*will identify cellular factors interacting with the viral genome and proteins,*as well as host proteins that are incorporated into viral particles and*involved in modulation of viral infection. We will map the highly conserved and*potent antigenic epitopes of viral proteins, which are transiently exposed*during the process of virus entry and represent important targets for vaccine*design. These results will provide tools and directions for the continuation of*our research program in the investigation of intracellular trafficking of the viral*genome and proteins within the host cell, the mechanisms of viral assembly and*release, and the cellular pathways exploited and rearranged by nidoviruses to*facilitate infection and evade host surveillance. More importantly, our*findings will provide new specific targets for antiviral vaccine development. Our*findings will also be relevant to many other enveloped animal viruses. *** ***

猪繁殖与呼吸综合征病毒 (PRRSV) 和猪流行性腹泻病毒* (PEDV) 造成严重的农业经济损失，并被认为是加拿大和全世界主要的新出现的牲畜病原体。*这两种病毒都是单链、正链 RNA、有包膜的猪*巢病毒，具有共同特征，包括相似的特征。 粒子*结构、保守的基因组组织和复制策略。 *开发疫苗的传统方法并未产生可靠和*有效的疫苗，这些病毒仍然是全球养猪业的主要威胁。***我们认为，对巢状病毒与宿主相互作用的了解不足阻碍了针对巢状病毒的*有效疫苗的开发。因此，我们建议研究动物*巢病毒与宿主相互作用的分子机制，以确定新的抗病毒靶点并*制定有效的预防策略。***该计划的*长期目标是更好地了解动物*巢病毒与其宿主之间相互作用的分子*机制，以便*开发有效控制病毒感染的新策略。未来五年的短期目标是通过重点关注巢状病毒感染早期事件的表征和比较，阐明 PRRSV 和 PEDV 与宿主细胞的相互作用。为了实现这一目标，我们将：1）研究猪巢状病毒进入宿主细胞的细胞和分子机制，2）分析宿主细胞对病毒感染反应的蛋白质组图谱，表征巢状病毒的组成，并鉴定与病毒颗粒相关的宿主蛋白质。这些*具体目标的实现将有助于了解巢病毒感染最早阶段*病毒与宿主相互作用的本质。我们*将鉴定与病毒基因组和蛋白质相互作用的细胞因子，*以及纳入病毒颗粒和*参与调节病毒感染的宿主蛋白质。我们将绘制高度保守且*有效的病毒蛋白抗原表位，这些抗原表位在病毒进入过程中短暂暴露*，并代表疫苗*设计的重要目标。这些结果将为继续我们的研究计划提供工具和方向，以研究宿主细胞内病毒基因组和蛋白质的细胞内运输、病毒组装和释放的机制，以及巢状病毒利用和重新排列的细胞途径以促进感染和逃避宿主监视。更重要的是，我们*的发现将为抗病毒疫苗的开发提供新的具体目标。我们*的发现也与许多其他有包膜动物病毒相关。 *** ***