Bloc transmission of viruses and implications for viral dynamics

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，这些病毒使用溶酶体运出细胞。在使用溶酶体的过程中，这些病毒扰乱了溶酶体的功能。我们发现，这会导致包括抗原提呈在内的细胞生理学方面的严重缺陷，并可能导致观察到的临床异常。 其他可能的链病毒出口研究=--阻止病毒在水泡中的释放。 我们确定了当被阻断传播和单一粒子传播感染时宿主免疫反应(先天和获得性)的差异。综上所述，当细胞感染高多样性的病毒基因组时，我们发现它们不再能区分进入的非自身RNA和自身RNA分子，导致先天免疫反应的全面抑制。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识别的大部分了解。这项研究正在提交中。 我们还发现，在适应性免疫反应方面，特别是在其幼崽感染了游离病毒和含有囊泡的病毒的母亲的乳腺中的粘膜免疫反应方面，存在着深刻的差异。我们正在准备一份关于这项研究的手稿。

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.