Strongylocentrotus nudus egg polysaccharide (SEP) suppresses HBV replication via activation of TLR4-induced immune pathway

Chronic hepatitis B virus (HBV) infection is a worldwide public health problem that causes significant liverrelated morbidity and mortality. In our previous study, Strongylocentrotus nudus eggs polysaccharide (SEP), extracted from sea urchins, had immunomodulatory and antitumor effects. Whether SEP has anti-HBV activity is still obscure. This study demonstrated that SEP decreased the secretion of hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), as well as the replication and transcription of HBV both in vitro and in vivo. Immunofluorescence and immunohistochemistry results showed that the level of HBV core antigen (HBcAg) was clearly reduced by SEP treatment. Mechanistically, RT-qPCR, western blot, and confocal microscopy analysis showed that SEP significantly increased the expression of toll-like receptor 4 (TLR4) and co-localization with TLR4. The downstream molecules of TLR4, including NF-kappa b and IRF3, were activated and the expression of IFN-beta, TNF-alpha, IL-6, OAS, and MxA were also increased, which could suppress HBV replication. Moreover, SEP inhibited other genotypes of HBV and hepatitis C virus (HCV) replication in vitro. In summary, SEP could be investigated as a potential anti-HBV drug capable of modulating the innate immune.