tetano
Editor, Senior Moderator
PLoS One
. 2024 Aug 23;19(8):e0307450.
doi: 10.1371/journal.pone.0307450. eCollection 2024. RNA editing regulates host immune response and T cell homeostasis in SARS-CoV-2 infection
Molly Huang[SUP] 1 2 [/SUP], Adam Mark[SUP] 3 [/SUP], Jessica Pham[SUP] 4 [/SUP], Karina Vera[SUP] 1 [/SUP], Amanda M Saravia-Butler[SUP] 5 [/SUP], Afshin Beheshti[SUP] 6 7 8 [/SUP], Qingfei Jiang[SUP] 4 [/SUP], Kathleen M Fisch[SUP] 1 3 [/SUP]
Affiliations
Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection.
. 2024 Aug 23;19(8):e0307450.
doi: 10.1371/journal.pone.0307450. eCollection 2024. RNA editing regulates host immune response and T cell homeostasis in SARS-CoV-2 infection
Molly Huang[SUP] 1 2 [/SUP], Adam Mark[SUP] 3 [/SUP], Jessica Pham[SUP] 4 [/SUP], Karina Vera[SUP] 1 [/SUP], Amanda M Saravia-Butler[SUP] 5 [/SUP], Afshin Beheshti[SUP] 6 7 8 [/SUP], Qingfei Jiang[SUP] 4 [/SUP], Kathleen M Fisch[SUP] 1 3 [/SUP]
Affiliations
- PMID: 39178184
- PMCID: PMC11343423
- DOI: 10.1371/journal.pone.0307450
Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection.