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

猪繁殖与 呼吸道综合征病毒（PRRSV）和猪流行性腹泻病毒 （PEDV）造成严重的农业经济损失， 被认为是加拿大和世界范围内主要的新兴牲畜病原体。 两种病毒均为单链、正义RNA，有包膜， 巢状病毒和共同的特征，包括类似的颗粒 结构、保守的基因组组织和复制策略。的 开发疫苗的传统方法并没有产生可靠和 有效的疫苗，这些病毒仍然是猪的主要威胁 全世界的工业。 我们认为， 对巢状病毒与宿主相互作用的理解阻碍了 针对巢状病毒的有效疫苗。因此，我们建议从分子水平上研究动物免疫的机制， 巢病毒-宿主相互作用，以鉴定新的抗病毒靶点， 制定有效的预防战略。 的 该计划的长期目标是更好地了解分子 动物巢状病毒与宿主相互作用的机制 开发有效控制病毒感染的新策略。短期 未来五年的目标是阐明PRRSV和PEDV的相互作用， 宿主细胞通过专注于早期事件的表征和比较 巢状病毒感染。为了实现这一目标，我们将：1）调查 猪巢状病毒侵入宿主的细胞和分子机制 细胞，和2）分析宿主细胞对病毒应答的蛋白质组学谱 感染，表征巢状病毒的组成，并鉴定宿主 与病毒颗粒相关的蛋白质。完成这些 具体的目标将导致理解的性质 病毒-宿主相互作用在巢病毒感染的最早阶段。我们 将识别与病毒基因组和蛋白质相互作用的细胞因子， 以及掺入病毒颗粒中的宿主蛋白质， 参与调节病毒感染。我们将绘制高度保守的 瞬时暴露的病毒蛋白的有效抗原表位 在病毒进入过程中，是疫苗的重要靶点 设计这些结果将为继续开展 我们的研究计划在调查细胞内运输的病毒 宿主细胞内的基因组和蛋白质，病毒组装的机制， 释放，以及巢状病毒利用和重排的细胞途径， 便于感染和逃避宿主监视。更重要的是我们 这些发现将为抗病毒疫苗的开发提供新的特异性靶点。我们 这些发现也将与许多其他有包膜的动物病毒有关。

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.