Innate and Adaptive Immunity of Murine Neural Stem Cell-Derived piRNA Exosomes/Microvesicles against Pseudotyped SARS-CoV-2 and HIV-Based Lentivirus

By testing pseudotyped SARS-CoV-2 and HIV-based lentivirus, this study reports that exosomes/microvesicles (Ex/Mv) isolated from murine hypothalamic neural stem/progenitor cells (htNSC) or subtype htNSCPGHM as well as hippocampal NSC have innate immunity-like actions against these RNA viruses. These extracellular vesicles also have a cell-free innate antiviral action by attacking and degrading viruses. We further generated the induced versions of Ex/Mv through prior viral exposure to NSCs and found that these induced Ex/Mv were stronger than basal Ex/Mv in reducing the infection of these viruses, suggesting the involvement of an adaptive immunity-like antiviral function. These NSC Ex/Mv were found to be characterized by producing large libraries of P element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) against genomes of various viruses, and some of these piRNAs were enriched during the adaptive immunity-like reaction, possibly contributing to the antiviral effects of these Ex/Mv. In conclusion, NSC Ex/Mv have antiviral immunity and could potentially be developed to combat against various viruses.