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Objective: Several studies have shown that rituximab may enhance hepatitis C virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the host immune response in HCV infection; miRNAs can be packaged into the exosomes and then shuttled by the exosomes to aid biologic functions. However, the role of exosomal miRNAs (exo‐miRNAs) in rituximab‐related HCV activity enhancement remains unclear. Methods: The association between rituximab and increased HCV activity was examined using an in vitro cell‐based assay. Purified exosomes were confirmed using immunoblotting and flow cytometry and quantified using enzyme‐linked immunosorbent assay. Exosomal miRNA‐155 (exo‐miR‐155) levels were measured using quantitative reverse transcription–polymerase chain reaction. Results: In vitro data showed that B cell–derived miR‐155 could inhibit HCV replication in hepatocytes through exosome transmission. Rituximab could both induce B cell depletion and affect intracellular miR‐155 production as well as exo‐miR‐155 transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum exosome levels were increased in rheumatoid arthritis (RA) patients with HCV infection compared with the levels in RA patients without HCV infection (P < 0.01). The exo‐miR‐155 levels were significantly increased in RA patients with HCV infection compared with those without infection (P < 0.01). A significantly greater decrement of exo‐miR‐155 expression was observed after rituximab therapy compared with those observed before therapy (P < 0.01), and hepatitis C viral loads increased simultaneously (P < 0.05). Conclusion: Circulating exo‐miR‐155 levels were negatively correlated with hepatitis C viral loads and subsequently associated with rituximab‐related HCV activity enhancement in RA patients. Exo‐miR‐155 may become a potential diagnostic biomarker or therapeutic target. [ABSTRACT FROM AUTHOR]

Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secreting neurons and glial cells. Investigating the susceptibility of these hESCs-derived neural cells to neurotrophic viruses, such as Japanese encephalitis virus (JEV), provides insight into the viral cell tropism in the infected human brain. We demonstrate that hESC-derived NPCs are highly vulnerable to JEV infection at a low multiplicity of infection (MOI). In addition, glial fibrillary acid protein (GFAP)-expressing glial cells are also susceptible to JEV infection. In contrast, only a few mature neurons were infected at MOI 10 or higher on the third day post-infection. In addition, functional neurotransmitter-secreting neurons are also resistant to JEV infection at high MOI. Moreover, we discover that vimentin intermediate filament, reported as a putative neurovirulent JEV receptor, is highly expressed in NPCs and glial cells, but not mature neurons. These results indicate that the expression of vimentin in neural cells correlates to the cell tropism of JEV. Finally, we further demonstrate that membranous vimentin is necessary for the susceptibility of hESC-derived NPCs to JEV infection. [ABSTRACT FROM AUTHOR]

Mixed cryobulinemia (MC) is the most common chronic hepatitis C virus (HCV)-associated extrahepatic manifestation. C-type lectin 18 (CLEC18) is a novel secretory lectin that is abundantly expressed in hepatocytes and peripheral blood cells (PBCs). We investigated the associations between CLEC18 expression during HCV infection and the presence of extrahepatic manifestations. A total of 41 rheumatic patients with HCV infection (including 28 patients with MC syndrome), 45 rheumatic patients without infection, and 14 healthy subjects were enrolled. The CLEC18 levels in PBCs and serum were determined by using flow cytometry and enzyme-linked immunosorbent assay, respectively. Significantly higher CLEC18 levels were observed in patients with HCV infection (P < 0.001) and were positively correlated with HCV viral loads (γ = 0.56, P < 0.05). Among patients with HCV infection, significantly increased CLEC18 levels were observed in patients with MC syndrome, particularly in those with type II MC (P < 0.05). CLEC18 levels were associated with cryoglobulin and C4 levels (P < 0.05). CLEC18 was significantly associated with HCV infection, particularly in those with HCV-associated MC. CLEC18 levels were also positively correlated with MC disease activity, suggesting its involvement in MC pathogenesis. CLEC18 may be a novel indicator of HCV infection and a potential therapeutic target in rheumatic patients. [ABSTRACT FROM AUTHOR]