Title: Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12.

Authors: Teng, Yun; Xu, Fangyi; Zhang, Xiangcheng; Mu, Jingyao; Sayed, Mohammed; Hu, Xin; Lei, Chao; Sriwastva, Mukesh; Kumar, Anil; Sundaram, Kumaran; Zhang, Lifeng; Park, Juw Won; Chen, Shao-Yu; Zhang, Shuangqin; Yan, Jun; Merchant, Michael L; Zhang, Xiang; McClain, Craig J; Wolfe, Jennifer K; Adcock, Robert S; Chung, Donghoon; Palmer, Kenneth E; Zhang, Huang-Ge

Published In Mol Ther, (2021 08 04)

Abstract: Lung inflammation is a hallmark of coronavirus disease 2019 (COVID-19). In this study, we show that mice develop inflamed lung tissue after being administered exosomes released from the lung epithelial cells exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp12 and Nsp13 (exosomesNsp12Nsp13). Mechanistically, we show that exosomesNsp12Nsp13 are taken up by lung macrophages, leading to activation of nuclear factor κB (NF-κB) and the subsequent induction of an array of inflammatory cytokines. Induction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β from exosomesNsp12Nsp13-activated lung macrophages contributes to inducing apoptosis in lung epithelial cells. Induction of exosomesNsp12Nsp13-mediated lung inflammation was abolished with ginger exosome-like nanoparticle (GELN) microRNA (miRNA aly-miR396a-5p. The role of GELNs in inhibition of the SARS-CoV-2-induced cytopathic effect (CPE) was further demonstrated via GELN aly-miR396a-5p- and rlcv-miR-rL1-28-3p-mediated inhibition of expression of Nsp12 and spike genes, respectively. Taken together, our results reveal exosomesNsp12Nsp13 as potentially important contributors to the development of lung inflammation, and GELNs are a potential therapeutic agent to treat COVID-19.

PubMed ID: 33984520

MeSH Terms: No MeSH terms associated with this publication