Chronic viral infection is a significant burden on healthcare systems worldwide. Robust anti-viral immune responses are essential for viral clearance. Persistent viruses use a variety of mechanisms to evade immune surveillance including the upregulation of host immunesuppressive factors. Secreted fibrinogen-like protein 2 (FGL2) has been identified as an inhibitory effector molecule in suppressing immune responses in patients with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) disease. In a murine model of chronic infection caused by Lymphocytic choriomeningitis virus (LCMV) clone 13, we demonstrate that mice deficient in Fgl2 have increased numbers of mature antigen-presenting cells (APC), improved virus-specific cytotoxic T cell immunity and enhanced viral clearance when compared to wild-type mice. These results highlight the importance of the FGL2 inhibitory pathway in immune evasion and provide a rationale to investigate the effects of blocking FGL2 as a novel immune therapeutic in patients suffering from persistent infections.

Chronic viral infection is a significant burden on healthcare systems worldwide. Robust anti-viral immune responses are essential for viral clearance. Persistent viruses use a variety of mechanisms to evade immune surveillance including the upregulation of host immunesuppressive factors. Secreted fibrinogen-like protein 2 (FGL2) has been identified as an inhibitory effector molecule in suppressing immune responses in patients with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) disease. In a murine model of chronic infection caused by Lymphocytic choriomeningitis virus (LCMV) clone 13, we demonstrate that mice deficient in Fgl2 have increased numbers of mature antigen-presenting cells (APC), improved virus-specific cytotoxic T cell immunity and enhanced viral clearance when compared to wild-type mice. These results highlight the importance of the FGL2 inhibitory pathway in immune evasion and provide a rationale to investigate the effects of blocking FGL2 as a novel immune therapeutic in patients suffering from persistent infections.