Identification of new type I interferon-stimulated genes and investigation of their involvement in IFN-β activation

Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-β promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-β activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-β signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.

The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection

Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77-113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving α-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.

Therapeutic effect of captopril on aged patients with essential hypertension and complications / 心血管康复医学杂志

Objective:To observe therapeutic effect of captopril treatment on aged patients with essential hyperten‐sion (EH) and complications and evaluate its safety .Methods :A total of 116 aged EH patients ,who were compli‐cated with dyslipidemia ,diabetes mellitus etc . were selected from our hospital .According to random number table , they were randomly and equally divided into atenolol control group and captopril group (received captopril based on treatment of atenolol control group) .Blood pressure ,heart rate ,fasting plasma glucose (FPG) and blood lipids were observed and compared between two groups ,the therapeutic effect and adverse reactions were assessed .Re‐sults:After treatment ,total effective rate of captopril group was significantly higher than that of atenolol control group (98.28% vs .87.93% ,P<0.05);compared with atenolol control group ,there were significant reductions in levels of blood pressure [ (131.20 ± 11.02/82.01 ± 6.75) mmHg vs .(115.62 ± 10.27/75.68 ± 5.21) mmHg] ,heart rate [ (65.14 ± 6.32) beats/min vs .(57.21 ± 4.02) beats/min] ,FPG [ (4.75 ± 1.36) mmol vs .(3.65 ± 1.24) mmol] ,total cholesterol [ (2.69 ± 0.58) mmol/L vs .(2.10 ± 0.41) mmol/L] ,triglyceride [ (0.96 ± 0.41) mmol/L vs .(0.72 ± 0.35) mmol/L] and low density lipoprotein cholesterol [ (1.95 ± 0.57) mmol/L vs .(1.71 ± 0.40) mmol/L] in captopril group ,P<0.05 or <0.01 .There were no obvious adverse reactions occurred in both groups . Conclusion:Compared with atenolol ,captopril treatment possesses better therapeutic effect without adverse reac‐tions in aged patients with essential hypertension and complications ,which is worth extending .

TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope

Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.