A non-canonical mechanism of antiviral activity of Oligoadenylate Synthetase 1

• Published in: The Journal of immunology (1950) Vol. 212; no. 1_Supplement; pp. 120 - 120_4401
• Main Authors: Harioudh, Munesh, Perez, Joseph, Chong, Zhenlu, Nair, Sharmila, So, Lomon, McCormick, Kevin, Ghosh, Arundhati, Shao, Lulu, Srivastava, Rashmi, Soveg, Frank, Ebert, Thomas, Atianand, Maninjay, Hornung, Veit, Savan, Ram, Diamond, Michael, Sarkar, Saumendra
• Format: Journal Article
• Language: English
• Published: 01.05.2024
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.212.supp.0120.4401

The translational arrest of protein synthesis is often a cellular response to the virus infection. However, some antiviral proteins continue to be translated through unknown mechanisms during this translational shutdown. Here, we report a mechanism by which antiviral effectors are upregulated during this translational shutdown. We found that interferon (IFN) stimulated gene, Oligoadenylate Synthetase 1 (OAS1), binds AU-rich elements (ARE) of specific mRNA, including IFNβ, prolonging the half-life and continued expression. This increased IFN expression protects from WNV infection in vitro and in vivo via downstream IFNAR signaling. This mechanism is common between human OAS1 and mouse Oas1b, independent of OAS enzyme activity and RNase L. However, human OAS1 inhibits SARS-CoV-2 replication through its canonical enzyme activity via RNase L, thus establishing two different mechanisms of OAS1 antiviral activity. These results establish OAS1 as an ARE-binding protein with a broader non-canonical function that protects IFN expression from translational shutdown.