Search

Background: Dengue virus (DENV) is found in the tropical and subtropical regions and affects millions of people annually. Currently, no specific vaccine or antiviral treatment against dengue virus is available. Innate immunity has been shown to be important for host resistance to DENV infection. Although protein kinase regulated by double-stranded RNA (PKR) has been found to promote the innate signaling in response to infection by several viruses, its role in the innate response to DENV infection is still unclear. Our study aimed to investigate the role of PKR in DENV-induced innate immune responses. Methodology/Principal Findings: By RNAi, silencing of PKR significantly enhanced the expression of interferon (IFN)-b in DENV infected human lung epithelial A549 cells. Western blot and immunofluorescence microscopy data showed that PKR knockdown upregulated the activation of innate signaling cascades including p38 and JNK mitogen-activated protein kinases (MAPKs), interferon regulatory factor-3 and NF-κB, following DENV2 infection. Likewise, a negative regulatory effect of PKR on the IFN production was also observed in poly(IC) challenged cells. Moreover, the PKR knockdown-mediated IFN induction was attenuated by RIG-I or IPS-1 silencing. Finally, overexpression of a catalytically inactive PKR mutant (K296R), but not of a mutant lacking dsRNA binding activity (K64E) or the double mutant (K64EK296R), reversed the IFN induction mediated by PKR knockdown, suggesting that the dsRNA binding activity is required for PKR to downregulate IFN production. Conclusions/Significance: PKR acts as a negative regulator of IFN induction triggered by DENVs and poly(IC), and this regulation relies on its dsRNA binding activity. These findings reveal a novel regulatory role for PKR in innate immunity, suggesting that PKR might be a promising target for anti-DENV treatments. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) utilizes host factors throughout its life cycle. In this study, we identified RNA helicase A (RHA), a member of the DEAD/H helicase family, as an important host factor of DENV. In response to DENV2 infection, nuclear RHA protein was partially redistributed into the cytoplasm. The short interfering RNA-mediated knockdown of RHA significantly reduced the amounts of infectious viral particles in various cells. The RHA knockdown reduced the multistep viral growth of DENV2 and Japanese encephalitis virus but not Zika virus. Further study showed that the absence of RHA resulted in a reduction of both viral RNA and protein levels, and the data obtained from the reporter replicon assay indicated that RHA does not directly promote viral protein synthesis. RHA bound to the DENV RNA and associated with three nonstructural proteins, including NS1, NS2B3, and NS4B. Further study showed that different domains of RHA mediated its interaction with these viral proteins. The expression of RHA or RHA-K417R mutant protein lacking ATPase/helicase activity in RHA-knockdown cells successfully restored DENV2 replication levels, suggesting that the helicase activity of RHA is dispensable for its proviral effect. Overall, our work reveals that RHA is an important factor of DENV and might serve as a target for antiviral agents. [ABSTRACT FROM AUTHOR]

The nano-ZIF-8@GO hybrids were synthesized and blended with poly(lactic acid) (PLA) by solution method. The effect of nano-ZIF-8@GO hybrids on the crystallization was investigated by DSC and POM. The results showed that low addition amount of nano-ZIF-8@GO had a significant influence on the crystallization behavior of PLA. The tensile strength and elongation at break of the PLA/ZIF-8@GO nanocomposites with 0.5 wt% of ZIF-8@GO were increased to 49.63 MPa and 24.10% compared with 35.83 MPa and 17.66% of the pure PLA, respectively. The addition of nano-ZIF-8@GO hybrids also enhanced the flame retardancy of PLA, and the mechanism was proposed. [ABSTRACT FROM AUTHOR]

Abstract: A practical spatio-temporal database (STDB) technique for dynamic urban land management is presented. One of the STDB models, the expanded model of Base State with Amendments (BSA), is selected as the basis for developing the dynamic cadastral management technique. Two approaches, the Section Fast Indexing (SFI) and the Storage Factors of Variable Granularity (SFVG), are used to improve the efficiency of the BSA model. Both spatial graphic data and attribute data, through a succinct engine, are stored in standard relational database management systems (RDBMS) for the actual implementation of the BSA model. The spatio-temporal database is divided into three interdependent sub-databases: present DB, history DB and the procedures-tracing DB. The efficiency of database operation is improved by the database connection in the bottom layer of the Microsoft SQL Server. The spatio-temporal system can be provided at a low-cost while satisfying the basic needs of urban land management in China. The approaches presented in this paper may also be of significance to countries where land patterns change frequently or to agencies where financial resources are limited. [Copyright &y& Elsevier]