Interleukin-34 inhibits hepatitis B virus replication in vitro and in vivo

Abstract

BackgroundThe hepatitis B virus (HBV) infection could activate the immune system and induce extensive inflammatory response. As the most important inflammatory factor, interleukins are critical for anti-viral immunity. Here we investigated whether interleukin-34 (IL-34) play a role in HBV infection.Methodology/Principal findingsIn this study, we first found that both serum IL-34 and IL-34 mRNA in PBMCs in chronic HBV patients was significantly decreased compared to the healthy controls. Furthermore, both IL-34 protein and mRNA levels were declined hepatoma cells expressing HBV. In addition, the clinical parameters analysis found that serum IL-34 was significantly associated with HBV DNA (P = 0.0066), ALT (P = 0.0327), AST (P = 0.0435), TB (P = 0.0406), DB (P = 0.0368) and AFP (P = 0.0225). Correlation analysis also found that serum IL-34 negatively correlated with HBV DNA copies, ALT and AST. In vitro studies found that IL-34 treatment in HepAD38 and HepG2.2.15 cells markedly inhibited HBV DNA, total RNA, 3.5kb mRNA and HBc protein. In vivo studies further demonstrated IL-34 treatment in HBV transgenic mice exhibited greater inhibition on HBV DNA, total RNA, 3.5kb mRNA and HBc protein, suggesting the effect to IL-34 on HBV is likely due to host innate or adaptive immune response.Conclusions/SignificanceOur study identified a novel interleukin, IL-34, which has anti-viral activity in HBV replication in hepatocytes in vitro and in vivo. These data suggest a rationale for the use of IL-34 in the HBV treatment.

Interleukin‐34 mediated by hepatitis B virus X protein via CCAAT/enhancer‐binding protein α contributes to the proliferation and migration of hepatoma cells

“…IL‐34 is considered to be associated with HBV infection and HCC . However, the role and associated mechanisms of IL‐34 in HBV‐related HCC are not well clarified.…”

“…12,13 Importantly, recent studies show that IL-34 is involved in the HBV infection and associated with liver fibrosis. 14,15 Besides, the report from Zhou S et al shows that increased IL-34 is related to the poor survival and tumour recurrence in HCC patients, and modulates the invasion and metastasis of HCC cells via macrophages. 16 However, whether IL-34 contributes to the development of HBV-infected HCC is still unclear.…”

“…Until now, collective evidence has demonstrated that IL‐34 is involved in the development of viral infection, autoimmune diseases and cancers . Importantly, recent studies show that IL‐34 is involved in the HBV infection and associated with liver fibrosis . Besides, the report from Zhou S et al shows that increased IL‐34 is related to the poor survival and tumour recurrence in HCC patients, and modulates the invasion and metastasis of HCC cells via macrophages .…”

Interleukin-34, a comprehensive review

“…Since IL‐34 is expressed at mRNA level in various tissues, this expression is expected to be changed under pathological conditions. Indeed, several studies have confirmed the enhancement of IL‐34 expression at mRNA and protein levels in the context of various diseases including autoimmune disorders, inflammation, infections, metabolic diseases, neurological disorders, and cancer . At the cellular level, IL‐34‐producing cells include synovial fibroblasts, immune cells, epithelial cells, endothelial cells, adipocytes, and cancer cells.…”

The roles of CSFs on the functional polarization of tumor‐associated macrophages

“…An overexpression of IL-34 has been reported in some severe diseases associated with chronic inflammation, such as viral infections [37,77], inflammatory bowel diseases [78], rheumatoid arthritis [76,79], systemic lupus erythematosus [80], and Sjogren's syndrome [81]. In contrast, one study has reported a decrease in IL-34 expression in patients chronically infected by hepatitis B virus [82].…”