[P007] Poster

12:10 PM - 1:00 PM JST(3:10 AM - 4:00 AM UTC)

[P04-491] Engineering a cell membrane-based biomaterials platform for CXCR3 receptor expression to target COVID-19

○Ni-Shan Cheng¹, Chun-Hsiang Chiu², Chih-Hsuan Tsai¹ (1. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University (Taiwan), 2. Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University (Taiwan))

Keywords:

COVID-19,SARS-CoV-2,IP-10,chemokine,extracellular vesicle,pseudovirus,baculovirus

Human coronaviruses (HCoVs) cause respiratory infections and can be differentiated into strains leading to severe and mild symptoms. Severe HCoV strains, including SARS-CoV-2 (the pathogen of COVID-19), SARS-CoV, and MERS-CoV, can lead to death through inducing excessive inflammatory responses, in which CXCL10 (IP-10), an inflammatory chemokine, is strongly associated with disease severity and poor prognosis. Since IP-10 binds to its receptor CXCR3 to amplify inflammatory responses, inhibiting this pathway may be a potential therapeutic strategy. Therefore, we aimed to produce extracellular vesicles containing CXCR3 (CXCR3-EVs) to intercept excess IP-10 and assess their potential to alleviate inflammation. To facilitate the study, we constructed pseudoviruses N-Bac and S-Bac by displaying the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 on the surface of baculoviruses to simulate the dangerous SARS-CoV-2 virus. Transduction of the N-Bac and S-Bac into A549 cells stimulated the expression of IP-10 mRNA and protein. Adding a recombinant CXCR3 protein successfully reduced the expression of IP-10-downstream inflammatory genes. CXCR3-EVs were generated by CXCR3 plasmid transfection in HEK293T and isolated using an exosome isolation reagent. Adding CXCR3-EVs also reduced the expression of IP-10-downstream inflammatory proteins in cells transduced with N-Bac or S-Bac. Notably, adding CXCR3-EVs did not increase inflammatory cytokine levels, indicating their safety for cells. In summary, targeting IP-10 using CXCR3 protein has therapeutic potential to alleviate inflammation caused by severe HCoV, and incorporating CXCR3 into EVs is not only easier to produce but also has better efficacy and safety.