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

猪的繁殖和繁殖 呼吸综合征病毒(PRRSV)和猪流行性腹泻病毒 (PEDV)对严重的农业经济损失负有责任，并 被认为是加拿大和世界范围内的主要新兴牲畜病原体。 这两种病毒都是单链、正义RNA，包膜猪 和NidoVirus的共同特征，包括相似的颗粒 结构，保守的基因组组织和复制策略。这个 传统的疫苗开发方法并没有产生可靠和 有效的疫苗，这些病毒仍然是对猪的主要威胁 世界范围内的工业。 我们认为，这是不够的 对NID病毒-宿主相互作用的了解阻碍了NIDV的发展 针对NidoVirus的有效疫苗。因此，我们建议对动物的分子机制进行研究。 NidVirus-宿主相互作用，以确定新的抗病毒靶点和 制定有效的预防策略。 这个 这项计划的长期目标是更好地了解分子 动物NIDO病毒与宿主的有序相互作用机制 制定有效控制病毒感染的新战略。短期内 未来五年的目标是阐明PRRSV和PEDV与 通过专注于早期事件的特征和比较来寄主细胞 在尼诺氏病毒感染中。为了达到这一目标，我们将：1)调查 猪NIDV侵入宿主的细胞和分子机制 细胞，以及2)分析宿主细胞对病毒的反应的蛋白质组学 感染，表征NidoVirus的组成，并识别宿主 与病毒颗粒相关的蛋白质。实现这些目标 具体的目标将导致对 NidVirus感染早期病毒与宿主的相互作用。我们 将识别与病毒基因组和蛋白质相互作用的细胞因子， 以及被整合到病毒颗粒中的宿主蛋白 参与了病毒感染的调节。我们将绘制高度保守和 病毒蛋白的有效抗原表位，瞬时暴露 在病毒进入过程中，代表着疫苗的重要靶点 设计。这些成果将为继续开展这项工作提供工具和方向 我们在调查病毒在细胞内传播方面的研究计划 宿主细胞内的基因组和蛋白质，病毒组装和 释放，以及被NidoVirus利用和重排的细胞途径 促进感染并逃避宿主监视。更重要的是，我们的 这些发现将为抗病毒疫苗的开发提供新的特定靶点。我们的 这些发现也将与许多其他被包膜的动物病毒相关。

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.