PT  - JOURNAL ARTICLE
AU  - Shoeb Ikhlas
AU  - Afia Usman
AU  - Dongkyeong Kim
AU  - Dongsheng Cai
TI  - Exosomes/microvesicles target SARS-CoV-2 via innate and RNA-induced immunity with PIWI-piRNA system
AID  - 10.26508/lsa.202101240
DP  - 2022 Mar 01
TA  - Life Science Alliance
PG  - e202101240
VI  - 5
IP  - 3
4099  - https://www.life-science-alliance.org/content/5/3/e202101240.short
4100  - https://www.life-science-alliance.org/content/5/3/e202101240.full
SO  - Life Sci. Alliance2022 Mar 01; 5
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 SARS-CoV-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.