Ficolins and infectious diseases

Ficolins are serum complement lectins,with a structure similar to mannose-binding lectin(MBL) and lung surfactant protein(SP)-A and SP-D.Ficolins activate the lectin complement system and play important roles in host innate immunity.Ficolins are members of the collectin family of proteins,which act as pattern recognition receptors(PRRs).They are soluble oligomeric defense proteins with lectin-like activity,and are able to recognize pathogen-associated molecular patterns(PAMPs),which are carbohydrate molecules on the surface of pathogens,and of apoptotic,necrotic,and malignant cells.Upon binding to their specific PAMPs,ficolins may trigger activation of the immune system either(1) by initiating activation of complement via the lectin pathway,(2) by a primitive type of opsonophagocytosis,or(3) by stimulating secretion of the inflammatory cytokines interferon(IFN)-y,interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-a,and production of nitric oxide(NO)by macrophages,thus limiting the infection and concurrently orchestrating the subsequent adaptive immune response.Recently,a number of reports have shown that dysfunction or abnormal expression of ficolins may play crucial roles in viral and bacterial diseases and in inflammation.This review summarizes the reports on the roles of ficolins in the infectious diseases,and provides insight into ficolins as novel innate immune therapeutic options to treat these diseases.

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.

Lnc-RP5 Regulates the mi R-129-5p/Notch1/PFV Internal Promoter Axis to Promote the Expression of the Prototype Foamy Virus Transactivator Tas

Prototype foamy virus(PFV)is a unique retrovirus that infects animals and humans and does not cause clinical symptoms.Long noncoding RNAs(lncRNAs)are believed to exert multiple regulatory functions during viral infections.Previously,we utilized RNA sequencing(RNA-seq)to characterize and identify the lncRNA lnc-RP5-1086 D14.3.1-1:1(lnc-RP5),which is markedly decreased in PFV-infected cells.However,little is known about the function of lnc-RP5 during PFV infection.In this study,we identified lnc-RP5 as a regulator of the PFV transcriptional transactivator(Tas).Lnc-RP5 enhanced the activity of the PFV internal promoter(IP).The expression of PFV Tas was found to be promoted by lnc-RP5.Moreover,mi R-129-5 p was found to be involved in the lnc-RP5-mediated promotion of PFV IP activity,while the Notch1 protein suppressed the activity of PFV IP and the expression of Tas.Our results demonstrate that lnc-RP5 promotes the expression of PFV Tas through the miR-129-5 p/Notch1/PFV IP axis.This work provides evidence that host lnc RNAs can manipulate PFV replication by employing mi RNAs and proteins during an early viral infection.