ABSTRACT
Understanding the pathogenesis of SARS-CoV-2 is crucial to respond to the current coronavirus disease 2019 (COVID-19) pandemic. Sputum samples from 20 COVID-19 patients and healthy controls were collected, respectively. During the isolation of infectious SARS-CoV-2 virus, EV-like vesicles were associated with virions under a transmission electron microscope. Next, the expression of IL6 and TGF-β increased in EVs derived from the sputum of patients, and these were highly correlated with the expression of the SARS-CoV-2 N protein. Further, proximity barcoding assay (PBA) was used to investigate the immune-related proteins in the EVs, and the relationship between EVs and SARS-CoV-2 N protein in COVID-19 patients’ samples. Particularly, to investigate the differential contribution of the specific EV subsets, the protein expression of a single EV was detected and analyzed for the first time. Among the 40 EV subpopulations, 18 were found to have significant differences. The EV subpopulation regulated by CD81 were most likely to correlate with the changes in the pulmonary microenvironment after SARS-CoV-2 infection. This study provides evidence on the association between EVs and the SARS-CoV-2 virus, give a deep insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of nanoparticles drug intervention in viral infection.
Subject(s)
COVID-19ABSTRACT
In response to the present coronavirus disease 2019 (COVID-19) pandemic, it is important to understand the infection pathogenesis of SARS-CoV-2. Sputum samples from 20 COVID-19 patients and healthy controls were collected, respectively. During the isolation of infectious SARS-CoV-2 virus, exosome-like vesicles were found associated with virions under transmission electron microscope. Next, the expression of IL6 and TGF-β increased in exosomes derived from the sputum of patients, and these were highly correlated with the expression of the SARS-CoV-2 N protein. Further, proximity barcoding assay (PBA) was used to investigate the immune related proteins in the exosomes, as well as the relationship between exosomes and SARS-CoV-2 N protein in COVID-19 patients’ samples. Particularly, to investigate the differential contribution of the specific exosome subsets, the protein expression of a single exosome was detected and analyzed for the first time. Among the 40 exosome subpopulations, 18 were found to have significant differences. The exosome subpopulation regulated by CD81 were most likely to correlate with the changes in the pulmonary microenvironment after SARS-CoV-2 infection. This study provides evidence on the association between exosomes and SARS-CoV-2 virus and promotes our understanding on possible pathogenesis of SARS-CoV-2 infection.Funding Statement: This work is supported by the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Guangdong province (2020B111133001), the China Postdoctoral Science Project (2020T130025ZX and 2019M652860), the National Key Research and Development Program of China (2016YFC1304101), the Independent project of the State Key Laboratory of Respiratory Diseases (SKLRD-QN-201913), and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S155).Declaration of Interests: The authors have declared that no conflict of interest exists.Ethics Approval Statement: The present study obtained the approval of the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (Guangzhou, China).