Inducible Rubicon facilitates viral replication by antagonizing interferon production

The RUN domain Beclin-1-interacting cysteine-rich-containing(Rubicon)protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner,but little is known regarding the role of Rubicon during viral infection.Here,we performed functional studies of the identified target in interferon(IFN)signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN.The Rubicon protein levels were elevated in peripheral blood mononuclear cells,sera and liver tissues from patients with hepatitis B virus(HBV)infection relative to those in healthy individuals.Assays of the overexpression and knockdown of Rubicon showed that Rubicon significantly promoted HBV replication.In addition,Rubicon knockdown resulted in the inhibition of enterovirus 71,influenza A virus and vesicular stomatitis virus.The expression o0f Rubicon led to the suppression of virus-induced type-I interferon(IFN-αand IFN-β)and type-III interferon(IFN-λ1).Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process,and the NF-κB essential modulator(NEMO),a key factor in the IFN pathway,was the target with which Rubicon interacted.Our results reveal a previously unrecognized function of Rubicon as a virus-induced protein that binds to NEMO,leading to the inhibition of type-I interferon production.Rubicon thus functions as an important negative regulator of the innate immune response,enhances viral replication and may play a role in viral immune evasion.

Serum ficolin-2 concentrations are significantly changed in patients with hepatitis B virus infection and liver diseases

Human ficolin-2 is an important lectin complement pathway activator that is secreted from liver cells and has been implicated as an anti-infection innate immune molecule. However, the role of ficolin-2 protein and its dynamic changes over the course of and in the prognosis of chronic hepatitis B(CHB) and hepatocellular carcinoma(HCC) remain unclear. In this study, we analyzed ficolin-2 protein expression in a cohort of individuals with CHB infection, HCC and cirrhosis. A sandwich enzyme-linked immunosorbent assay(ELISA) method was used to measure serum ficolin-2 concentrations. Ficolin-2 expression in liver tissues was detected by immunohistochemical staining. Serum ficolin-2 concentrations in CHB patients were significantly higher than in healthy controls and HBV carriers. After 48 weeks of routine amelioration liver function treatment, serum ficolin-2 concentrations decreased and were positively correlated with favorable alanine aminotransferase(ALT), HBV DNA and HBe Ag-seroconversion outcomes. Interestingly, we observed much lower expression of serum and intrahepatic ficolin-2 in HCC and cirrhosis compared with healthy controls. Our findings suggest that serum and intrahepatic ficolin-2 levels may be considered one of the indicators for the response of chronic HBV infection, HCC and cirrhosis.

Ficolin-2 binds to HIV-1 gp120 and blocks viral infection

Ficolin-2 is a lectin complement pathway activator present in normal human plasma and usually associated with infectious diseases, but little is known about the role of ficolin-2 in human immunodeficiency virus(HIV) infection. Here, we describe our novel findings that serum ficolin-2concentrations of 103 HIV-1 patients were much higher compared to those of 57 healthy donors. In vitro analysis showed that HIV-1 infection could enhance ficolin-2 expression. We further demonstrated that recombinant ficolin-2 protein could bind with HIV-1 envelope glycoprotein gp120, and subsequently induce complement dependent cytotoxicity. Moreover, ficolin-2 could block the entry of HIV-1 into target cells(TZM-b1 and MT-2 cells) and infection in a ficolin-2 dosedependent manner. To our knowledge, this is the first report about the protective role of ficolin-2against HIV-1 infection and our study suggests that ficolin-2 is an important human innate immune molecule against HIV.