TET2 is required for Type I IFN‐mediated inhibition of bat‐origin swine acute diarrhea syndrome coronavirus

Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered batorigin coronavirus with fatal pathogenicity for neonatal piglets. There is no vaccine to prevent SADS-CoV infection or clinically approved drugs targeting SADS-CoV.Therefore, unraveling cellular factors that regulate SADS-CoV for cell entry is critical to understanding the viral transmission mechanism and provides a potential therapeutic target for SADS-CoV cure. Here, we showed that Type I interferon (IFN-I) pretreatment potently blocks SADS-CoV entry into cells using lentiviral pseudovirions as targets whose entry is driven by the SADS-CoV Spike glycoprotein.IFN-I-mediated inhibition of SADS-CoV entry and replication was dramatically impaired in the absence of TET2. These results suggest TET2 is found to serve as a checkpoint of IFN-I-meditated inhibition on the cell entry of SADS-CoV, and our discovery might constitute a novel treatment option to combat against SADS-CoV.

Research Advances on Swine Acute Diarrhea Syndrome Coronavirus

“…None of the previously mentioned host critical factors were involved in promoting viral replication through the innate immunosuppression pathway in the current study. Only TET2, a protein expressed by host cells, has been reported to regulate SADS-CoV entry into cells by inhibiting the host cell immune pathway [143]. The mechanism of action of certain key host factors associated with SADS-CoV infection remains unclear.…”

Influenza A virus inhibits TET2 expression by endoribonuclease PA-X to attenuate type I interferon signaling and promote viral replication

“…These studies suggested that HIV could modulate TET2-dependent immune response and inflammation. Besides, TET2 has also been found to intervene in the infection of other viruses, including Epstein-Barr virus (EBV) [ 44 , 45 ] and swine acute diarrhea syndrome coronavirus (SADS-CoV) [ 46 ]. To date, whether IAV infection modifies TET2 expression and the role of TET2 in the immune response during IAV infection remains unclear.…”