Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.

IMPORTANCE: Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.

Predictive value of CD4+CD8+ double positive T cells for the severity of hemorrhagic fever with renal syndrome.

PURPOSES: We aimed to investigate the levels of CD4+CD8+ double positive (DP) T cells in patients with various severities of hemorrhagic fever with renal syndrome (HFRS), and the predictive capacity of DP T cells for the severity of this disorder. METHODS: The levels of DP T cells in 213 patients and 48 healthy donors were measured by flow cytometry, as were the levels of CD4+ T cells, CD8+ T cells, B lymphocytes, and natural killer (NK) cells. In each type of HFRS patient, we tested the basic clinical reference values for leukocytes, platelets, creatinine (Cr), uric acid (UA), and urea, and the values for activated partial thromboplastin time, prothrombin time, and fibrinogen, using conventional methods. The colloidal gold method was used to measure HFRS antibody levels in the patients. RESULTS: The frequency of DP T cells increased with disease severity and peaked in patients with critical disease. Furthermore, the level of DP T cells proportionally correlated with the levels of Cr, UA, and urea in the serum. In contrast, there was an inverse correlation between DP T cells and platelets. Interestingly, the pattern of change in DP T cell frequency was similar to those of CD8+ T cells, B cells, and NK cells, but an inverse tendency was observed for CD4+ T cells. DP T cells demonstrated significant predictive value for the severity of HFRS. CONCLUSIONS: The level of DP T cells is associated with HFRS severity, suggesting that it may be a potent indicator for the course of this disorder.

Potential clinical biomarkers in monitoring the severity of Hantaan virus infection.

Hantavirus, which causes hemorrhagic fever with renal syndrome (HFRS) is almost prevalent worldwide. While Hantaan virus (HTNV) causes the most severe form of HFRS with typical clinical manifestations of thrombocytopenia, increased vascular permeability, and acute kidney injury. Although the knowledge of the pathogenesis of HFRS is still limited, immune dysfunction and pathological damage caused by disorders of immune regulation are proposed to play a vital role in the development of the disorder, and the endothelium is considered to be the primary target of hantaviruses. Here, we reviewed the production and function of multiple molecules, mainly focusing on their role in immune response, endothelium, vascular permeability regulation, and platelet and coagulation activation which are closely related to the pathogenesis of HTNV infection. meanwhile, the relationship between these molecules and characteristics of HTNV infection including the hospital duration, immune dysfunction, thrombocytopenia, leukocytosis, and acute kidney injury are also presented, to provide a novel insight into the potential role of these molecules as monitoring markers for HTNV infection.

Aberrant expression of LncRNA CASC2 mediated the cell viability, apoptosis and autophagy of colon cancer cells by sponging miR-19a via NF-κB signaling pathway.

Abnormal and rapid proliferation of colon cancer cells is a severe problem that can be regulated by non-coding RNAs. Thus, our study focused on effects of lncRNA CASC2 and miR-19a on colon cancer cells. Expressions of lncRNA CASC2, miR-19a, Bcl-2, Bax and NF-κB/p65 were examined by RT-qPCR. Cell viabilities were detected by CCK-8. A luciferase report assay was used for measuring binding conditions between lncRNA CASC2 and miR-19a. Western blotting was used to evaluate expression of LC3-I, LC3-II and p62 related to autophagy. Expression of lncRNA CASC2 lower in cancer cell lines and the overexpression reduced the cell viability of HT29 and SW480. Furthermore, Bcl-2 was suppressed by overexpressed lncRNA CASC2, while Bax was upregulated. LC3-Ⅰ and p62 were both inhibited, but LC3-Ⅱ was promoted. MiR-19a was predicted to bind lncRNA CASC2 and expressed higher in cancer cell lines. Overexpressed miR-19a reduced expression of lncRNA CASC2 and increased cell viability. This was repressed by upregulated lncRNA CASC2. Bcl-2 and Bax expression and proteins implicated in autophagy that are regulated by lncRNA CASC2 upregulation were reversed by miR-19a overexpression. NF-κB was upregulated in colon cancer cell lines, while inhibition of NF-κB reversed functions of lncRNA CASC2 and magnified roles of miR-19a. Our findings showed that lncRNA CASC2 inhibited cell viability in colon cancer cell lines and miR-19a reversed its functions through the NF-κB signalling pathway, suggesting that these could be factors in treating colon cancer in the future.