Dipeptidyl peptidase-4 inhibitor sitagliptin significantly reduced hepatitis C virus replication in a diabetic patient with chronic hepatitis C virus infection

To the Editor：I have previously reported a type II diabetic patient complicated with chronic hepatitis C virus（HCV）infection.1]Recently,Riva et al[2]reported an association of truncated CXCL10 with failure to achieve spontaneous clearance of acute HCV infection.They showed that

Involvement of TLR2-My D88 in Abnormal Expression of mi R-146a in Peripheral Blood Monocytes of Patients with Chronic Hepatitis C

miR-146 a is an immunoregulatory micro RNA closely associated with viral infection. This study investigated the expression changes of mi R-146 a in peripheral blood monocytes of HCV-infected patients and the mechanism by which the THP-1 cells were stimulated with HCV core protein in vitro. It was found that in the peripheral blood monocytes of HCV-infected patients, mi R-146 a expression was upregulated. After treated by interferon/ribavirin, mi R-146 a expression was decreased when HCV RNA became undetectable. HCV core could directly stimulate THP-1 cells to produce mi R-146 a. Silencing TLR2 and My D88 could significantly inhibit the expression of mi R-146 a. It was concluded that the expression of mi R-146 a in peripheral blood monocytes of HCV-infected patients was abnormally increased. The TLR2-My D88 signaling pathway may take part in the overexpression of mi R-146 a in monocytes stimulated with HCV core protein.

Assays for RNA synthesis and replication by the hepatitis C virus

At least six major genotypes of Hepatitis C virus （HCV） cause liver diseases worldwide. The efficacy rates with current standard of care are about 50% against genotype 1, the most prevalent strain in the United States, Europe and Japan. Therefore more effective pan-genotypic therapies are needed. HCV RNA replication provides a number of validated targets for virus-specific and potentially pan-genotypic inhibitors. In vitro assays capturing the different steps of RNA synthesis are needed not only to identify new inhibitors, but also to examine their mechanisms of action. This review attempts to provide a comprehensive summary of the biochemical, cell-based and animal model systems to assess HCV polymerase activity and HCV RNA replication that should be useful for both basic research and applied studies.

Applications of phage-derived RNA-based technologies in synthetic biology

As the most abundant biological entities with incredible diversity,bacteriophages(also known as phages)have been recognized as an important source of molecular machines for the development of genetic-engineering tools.At the same time,phages are crucial for establishing and improving basic theories of molecular biology.Studies on phages provide rich sources of essential elements for synthetic circuit design as well as powerful support for the improvement of directed evolution platforms.Therefore,phages play a vital role in the development of new technologies and central scientific concepts.After the RNA world hypothesis was proposed and developed,novel biological functions of RNA continue to be discovered.RNA and its related elements are widely used in many fields such as metabolic engineering and medical diagnosis,and their versatility led to a major role of RNA in synthetic biology.Further development of RNA-based technologies will advance synthetic biological tools as well as provide verification of the RNA world hypothesis.Most synthetic biology efforts are based on reconstructing existing biological systems,understanding fundamental biological processes,and developing new technologies.RNA-based technologies derived from phages will offer abundant sources for synthetic biological components.Moreover,phages as well as RNA have high impact on biological evolution,which is pivotal for understanding the origin of life,building artificial life-forms,and precisely reprogramming biological systems.This review discusses phage-derived RNA-based technologies terms of phage components,the phage lifecycle,and interactions between phages and bacteria.The significance of RNA-based technology derived from phages for synthetic biology and for understanding the earliest stages of biological evolution will be highlighted.

Phosphatidylserine-Specific Phospholipase A1 is the Critical Bridge for Hepatitis C Virus Assembly

The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV assembly.Multiple regions of PLA1A were involved in their interaction and complex formation.Furthermore,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in cells.Meanwhile,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain 1.Interestingly,these amino acids in the sequence are also essential for viral RNA replication.Further experiments revealed that these four proteins interact with each other.Moreover,PLA1A expression levels were elevated in livers from HCV-infected patients.In conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly.