Schütz Desiree, Read Clarissa, Groß Rüdiger, Röcker Annika, Rode Sascha, Annamalai Karthikeyan, Fändrich Marcus, Münch Jan
Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Central Facility for Electron Microscopy, Ulm University, 89081 Ulm, Germany.
ACS Omega. 2021 Mar 9;6(11):7731-7738. doi: 10.1021/acsomega.1c00068. eCollection 2021 Mar 23.
Positively charged naturally occurring or engineered peptide nanofibrils (PNF) are effective enhancers of lentiviral and retroviral transduction, an often rate-limiting step in gene transfer and gene therapy approaches. These polycationic PNF are thought to bridge the electrostatic repulsions between negatively charged membranes of virions and cells, thereby enhancing virion attachment to and infection of target cells. Here, we analyzed PNF, which are formed by the peptide AL1, that represents a fragment of an immunoglobulin light chain that causes systemic AL amyloidosis. We found that negatively charged AL1 PNF interact with viral particles to a comparable extent as positively charged PNF. However, AL1 PNF lacked cell-binding activity, and consequently, did not enhance retroviral infection. These findings show that virion capture and cell binding of PNF are mediated by different mechanisms, offering avenues for the design of advanced PNF with selective functions.
带正电荷的天然存在或工程化的肽纳米纤维（PNF）是慢病毒和逆转录病毒转导的有效增强剂，而转导通常是基因转移和基因治疗方法中的限速步骤。这些聚阳离子PNF被认为可以桥接病毒粒子和细胞带负电荷的膜之间的静电排斥，从而增强病毒粒子对靶细胞的附着和感染。在此，我们分析了由肽AL1形成的PNF，该肽代表导致系统性AL淀粉样变性的免疫球蛋白轻链的一个片段。我们发现，带负电荷的AL1 PNF与病毒颗粒的相互作用程度与带正电荷的PNF相当。然而，AL1 PNF缺乏细胞结合活性，因此，不能增强逆转录病毒感染。这些发现表明，PNF的病毒粒子捕获和细胞结合是由不同机制介导的，为设计具有选择性功能的先进PNF提供了途径。
