Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Hamilton, MT, 59840, USA.
Cell Tissue Res. 2023 Apr;392(1):269-283. doi: 10.1007/s00441-021-03572-y. Epub 2022 Feb 2.
The properties of infectious prions and the pathology of the diseases they cause are dependent upon the unique conformation of each prion strain. How the pathology of prion disease correlates with different strains and genetic backgrounds has been investigated via in vivo assays, but how interactions between specific prion strains and cell types contribute to the pathology of prion disease has been dissected more effectively using in vitro cell lines. Observations made through in vivo and in vitro assays have informed each other with regard to not only how genetic variation influences prion properties, but also how infectious prions are taken up by cells, modified by cellular processes and propagated, and the cellular components they rely on for persistent infection. These studies suggest that persistent cellular infection results from a balance between prion propagation and degradation. This balance may be shifted depending upon how different cell lines process infectious prions, potentially altering prion stability, and how fast they can be transported to the lysosome. Thus, in vitro studies have given us a deeper understanding of the interactions between different prions and cell types and how they may influence prion disease phenotypes in vivo.
传染性朊病毒的特性以及它们引起的疾病的病理学取决于每种朊病毒株的独特构象。通过体内测定法研究了朊病毒疾病的病理学与不同菌株和遗传背景的相关性，但通过体外细胞系更有效地剖析了特定朊病毒株与细胞类型之间的相互作用如何导致朊病毒疾病的病理学。通过体内和体外测定法进行的观察不仅相互告知了遗传变异如何影响朊病毒特性，而且还告知了传染性朊病毒如何被细胞摄取、被细胞过程修饰和复制，以及它们依赖于持续感染的细胞成分。这些研究表明，持续性细胞感染是由朊病毒复制和降解之间的平衡决定的。这种平衡可能会根据不同的细胞系如何处理传染性朊病毒而改变，这可能会改变朊病毒的稳定性以及它们可以多快被运输到溶酶体。因此，体外研究使我们更深入地了解了不同朊病毒和细胞类型之间的相互作用，以及它们如何在体内影响朊病毒疾病表型。
