TY - JOUR
T1 - Exosomes/microvesicles target SARS-CoV-2 via innate and RNA-induced immunity with PIWI-piRNA system
AU - Ikhlas, Shoeb
AU - Usman, Afia
AU - Kim, Dongkyeong
AU - Cai, Dongsheng
N1 - Funding Information:
The authors thank Dr. Gary Whittaker (Cornell University) for providing the plasmid, Dr. Manoj S Nair, and Dr. David D Ho (Columbia University) for generously providing SARS-CoV-2 virus and BSL3 facility support as well as technical assistance, and Dr. Michael Schotsaert and Dr. Sonia Jangra (Icahn School of Medicine at Mount Sinai) for providing kind support and assistance. This study was supported partly by Einstein internal funds (to D Cai) and NIH AG031774, DK099136, HL147477, and DK121435 (all to D Cai).
Publisher Copyright:
© 2022 Rockefeller University Press. All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARSCoV- 2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.
AB - Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARSCoV- 2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.
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U2 - 10.26508/lsa.202101240
DO - 10.26508/lsa.202101240
M3 - Article
C2 - 34862272
AN - SCOPUS:85122149396
SN - 2575-1077
VL - 5
JO - Life Science Alliance
JF - Life Science Alliance
IS - 3
M1 - e202101240
ER -