Dynamics of viral infection

病毒感染动力学

• 批准号: 10702809
• 负责人: Gregoire Altan-Bonnet
• 金额: $ 22.28万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702809
• 关键词: 2019-nCoV; Antigen Presentation; Antigen Presentation Pathway; Antigens; Cells; Coronavirus; Coronavirus Infections; Cross Presentation; Defect; Family; Goals; Human; Image; Immune; Immune response; Immunologics; Immunology; Life Cycle Stages; Lysosomes; Methodology; Modality; Monitor; Monomeric GTP-Binding Proteins; Natural Killer Cells; Pathway interactions; Patients; RNA Viruses; Reporter; Severe Acute Respiratory Syndrome; T-Cell Activation; Virus; Virus Diseases; betacoronavirus; inhibitor; insight; interest; novel therapeutics; trafficking; virus envelope

Beta-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). While much is known regarding their cellular entry and replication pathways, their mode of egress remains uncertain; however, this is assumed to be via the biosynthetic secretory pathway by analogy to other enveloped viruses. Using imaging methodologies in combination with virus-specific reporters, we demonstrated that beta-Coronaviruses utilize lysosomal trafficking for egress from cells. This pathway is regulated by the Arf-like small GTPase Arl8b; thus, virus egress is insensitive to inhibitors of the biosynthetic secretory pathway. Coronavirus infection results in lysosome deacidification, inactivation of lysosomal degradation and disruption of antigen presentation pathways. This coronavirus-induced exploitation of lysosomes provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.

β-核纳病毒是包括严重急性呼吸综合征-COV2（SARS-COV2）的阳性链链RNA病毒家族。尽管他们的细胞进入和复制途径已知，但它们的出口方式仍然不确定。但是，通过类比与其他包膜病毒相比，假定这是通过生物合成分泌途径。 使用成像方法与病毒特异性记者结合使用，我们证明了β-核可纳病毒利用溶酶体运输从细胞出口。该途径受ARF样的小GTPase ARL8B调节；因此，病毒出口对生物合成分泌途径的抑制剂不敏感。冠状病毒感染会导致溶酶体脱钩，溶酶体降解失活以及抗原表现途径的破坏。这种冠状病毒引起的溶酶体的剥削提供了对患者观察到的细胞和免疫异常异常的见解，并提出了新的治疗方式。