Interleukin-35 stimulates hepatitis B virus transcription and replication by targeting transcription factor HNF4α Tao, Na-Na and Gong, Rui and Chen, Xiang and He, Lin and Ren, Fang and Yu, Hai-Bo and Chen, Juan and Ren, Ji-Hua,, 99, 645-654 (2018), doi = https://doi.org/10.1099/jgv.0.001050, publicationName = Microbiology Society, issn = 0022-1317, abstract= Hepatitis B virus (HBV) infection is a major health problem worldwide. Interleukin-35 (IL-35) is a definite immunosuppressive cytokine belonging to the IL-12 family. Nevertheless, the role of IL-35 in HBV replication remains elusive. In this study, we found that the level of HBV DNA replicative intermediates detected by qPCR and Southern blotting analysis was significantly increased by rhIL-35 in a dose-dependent manner. Moreover, HBV 3.5 kb mRNA levels were up-regulated by rhIL-35. The HBV core protein level as well as the HBsAg and HBeAg secretion levels were also increased by rhIL-35. Moreover, a mechanistic study demonstrated that IL-35 promoted HBV replication by enhancing the HBV core promoter activity. Importantly, hepatocyte nuclear factor 4α (HNF4α) was probably the target of IL-35. Mutation of the HNF4α-binding site on HBV core promoter or silencing HNF4α abolished the enhancement of HBV replication induced by IL-35. Finally, rhIL-35 was able to increase HBV replication in HBV transgenic mice. Taken together, our findings demonstrated that IL-35 has a novel role in HBV replication., language=, type=