Dynamics of viral infection
Dynamics of viral infection
批准号:
10262609
负责人:
Gregoire Altan-Bonnet
金额:
$18.23万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
Antigen PresentationAntigen Presentation PathwayAntigensCellsCoronavirusCoronavirus InfectionsCross PresentationDefectFamilyGoalsHumanImageImmuneImmune responseImmunologicsImmunologyLife Cycle StagesLysosomesMethodologyModalityMonitorMonomeric GTP-Binding ProteinsNatural Killer CellsPathway interactionsPatientsRNA VirusesReporterSevere Acute Respiratory SyndromeT-Cell ActivationVirusVirus Diseasesinhibitor/antagonistinsightinterestnovel therapeuticstraffickingvirus envelope
中文摘要
乙型冠状病毒是一个正链包膜RNA病毒家族,包括严重急性呼吸综合征- cov2 (SARS-CoV2)。虽然对它们的细胞进入和复制途径了解很多,但它们的退出模式仍然不确定;然而,这被认为是通过生物合成分泌途径,类似于其他包膜病毒。利用成像方法结合病毒特异性报告者,我们证明了β -冠状病毒利用溶酶体运输从细胞中输出。该途径受arf样小GTPase ar18b调控;因此,病毒的输出对生物合成分泌途径的抑制剂不敏感。冠状病毒感染导致溶酶体脱酸、溶酶体降解失活和抗原呈递途径中断。这种冠状病毒诱导的溶酶体利用提供了对患者观察到的细胞和免疫异常的见解,并提出了新的治疗方式。
英文摘要
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.
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海外基金