Bloc transmission of viruses and implications for viral dynamics

病毒的块传播及其对病毒动态的影响

• 批准号: 10265880
• 负责人: Nihal Altan-Bonnet
• 金额: $ 192.74万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 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/10265880
• 关键词: Animals; Antigen Presentation; Cell physiology; Cells; Clinical; Coronavirus; Defect; Human; Immune response; In Vitro; Innate Immune Response; Lead; Lysosomes; Mammary gland; Manuscripts; Mothers; Mucosal Immune Responses; Pathway interactions; Population; Process; RNA; Research; Vesicle; Viral; Viral Genome; Virulence; Virus; adaptive immune response; in vivo; novel; particle; pup; transmission process; viral transmission

Coronavirus Egress Research- lysosomal release of viruses: We have identified as novel egress pathway exploited by coronaviruses. We have found that these viruses use lysosomes to be transported out of the cell. In the process of using lysosomes these viruses disrupt lysosomal function. We have found that this leads to profound defects in cell physiology including antigen presentation and may lead to the observed clinical abnormalities. Other posotive strand virus egress research=- en block release of viruses in vesicles. We identified differences in the host immune responses (innate and adaptive) when infected by bloc transmission versus single particle transmission. In summary when cells are infected with high multiplicities of viral genomes we find that they can no longer distinguish among entering non-self RNA and self RNA molecules, leading to an overall suppression of the innate immune response. This is a completely unexpected finding and upends much of what we know about innate immune responses and self/non-self RNA recognition. This study is now being submitted. We also found profound differences in the adaptive immune responses, specifically the mucosal immune response in the mammary glands of mothers whose pups were infected with free viruses versus vesicle-contained viruses. We are preparing a manuscript on this study.

冠状病毒出口研究-病毒的溶酶体释放： 我们已经确定了冠状病毒利用的新的出口途径。我们已经发现这些病毒利用溶酶体被运输出细胞。在使用溶酶体的过程中，这些病毒会破坏溶酶体功能。我们已经发现，这导致细胞生理学（包括抗原呈递）的严重缺陷，并可能导致观察到的临床异常。 其他阳性链病毒逸出研究=- en阻止囊泡中病毒的释放。 我们确定了宿主免疫反应（先天性和适应性）的差异时，感染块传输与单粒子传输。总之，当细胞被高多样性的病毒基因组感染时，我们发现它们不再能够区分进入的非自身RNA和自身RNA分子，导致先天免疫应答的总体抑制。这是一个完全出乎意料的发现，颠覆了我们对先天免疫反应和自我/非自我RNA识别的大部分认识。目前正在提交这项研究报告。 我们还发现了适应性免疫反应的深刻差异，特别是在其幼崽感染游离病毒与囊泡病毒的母亲的乳腺粘膜免疫反应。我们正在准备一份关于这项研究的手稿。