Deubiquitinase USP47 attenuates virus-induced type I interferon signaling.

The innate immune responses are tightly regulated to ensure effective clearance of invading pathogens and avoid excessive inflammation. Ubiquitination and deubiquitination are important post-translational modifications in antiviral immune responses. Here, we discovered deubiquitinase USP47 as a novel negative immune system regulator. Overexpression of USP47 repressed Sendai virus, poly(I:C) and poly(dA:dT)-induced ISRE and IFN-ß activation, along with reduced IFNB1 transcription and enhanced viral replication. Knockdown of USP47 expression had the opposite effects. Dual-luciferase and phosphorylation assays showed that USP47 targeted downstream of MAVS and upstream of TBK1. Additional co-immunoprecipitation assays suggested that USP47 interacted with TRAF3 and TRAF6. Importantly, USP47 removed K63-linked polyubiquitin chains from TRAF3 and TRAF6. Hence, we describe a novel modulator of the antiviral innate immune response, USP47, which removes K63-linked polyubiquitins from TRAF3 and TRAF6, leading to reduced type I IFN signaling.

Interferon-Inducible LINC02605 Promotes Antiviral Innate Responses by Strengthening IRF3 Nuclear Translocation.

Non-coding RNAs represent a class of important regulators in immune response. Previously, LINC02605 was identified as a candidate regulator in innate immune response by lncRNA microarray assays. In this study, we systematically analyzed the functions and the acting mechanisms of LINC02605 in antiviral innate immune response. LINC02605 was up-regulated by RNA virus, DNA virus, and type I IFNs in NF-κB and Jak-stat dependent manner. Overexpression of LINC02605 promotes RNA virus-induced type I interferon production and inhibited viral replication. Consistently, knockdown of LINC02605 resulted in reduced antiviral immune response and increased viral replication. Mechanistically, LINC02605 released the inhibition of hsa-miR-107 on the expression of phosphatase and tensin homolog (PTEN). By microRNA mimics and inhibitors, hsa-miR-107 was demonstrated to not only inhibit PTEN's expression but also negatively regulate the antiviral immune response. Knockdown of LINC02605 led to the reduction of PTEN expression both in mRNA and protein levels. Overexpression of LINC02605 had an opposite impact. Moreover, LINC02605 attenuated the serine 97 phosphorylation level of interferon regulatory factor 3 (IRF3) by promoting PTEN expression. Nucleoplasmic fragmentation assay showed that knocking down LINC02605 inhibited the nuclear translocation of IRF3, rendering the host cells more susceptible to viral invasion, while overexpression showed opposite effects. Therefore, LINC02605 is an induced lncRNA by viral infection and plays a positive feedback in antiviral immune response through modulating the nuclear translocation of IRF3.

UBL4A Augments Innate Immunity by Promoting the K63-Linked Ubiquitination of TRAF6.

Human UBL4A/GdX, encoding an ubiquitin-like protein, was shown in this study to be upregulated by viral infection and IFN stimulation. Then the functions of UBL4A in antiviral immune response were characterized. Overexpression of UBL4A promoted RNA virus-induced ISRE or IFN-ß or NF-κB activation, leading to enhanced type I IFN transcription and reduced virus replication. Consistently, knockdown of UBL4A resulted in reduced type I IFN transcription and enhanced virus replication. Additionally, overexpression of UBL4A promoted virus-induced phosphorylation of TBK1, IRF3, and IKKα/ß. Knockdown of UBL4A inhibited virus-induced phosphorylation of TBK1, IRF3, and IKKα/ß. Coimmunoprecipitation showed that UBL4A interacted with TRAF6, and this interaction was enhanced upon viral infection. Ubiquitination assays showed that UBL4A promoted the K63-linked ubiquitination of TRAF6. Therefore, we reveal a novel positive feedback regulation of UBL4A in innate immune response combating virus invasion by enhancing the K63-linked ubiquitination of TRAF6.

Transcriptome analysis identifies the potential roles of long non-coding RNAs during parainfluenza virus infection.

Parainfluenza virus infection is a common respiratory illness in children. Although lncRNAs are novel regulators of virus-induced innate immunity, a systemic attempt to characterize the differential expression of lncRNAs upon parainfluenza virus infection is lacking. In this report, we identify 207 lncRNAs and 166 mRNAs differentially expressed in SeV-infected HEK293T cells by microarray. The functional annotation analysis reveals that differentially regulated transcripts are predominantly involved in the host antiviral response pathway. The lncRNAs with the potential to regulate SeV-induced antiviral response are identified by building the lncRNA-mRNA coexpression network. Furthermore, silencing lncRNA ENST00000565297 results in reduced type I IFN signaling upon SeV infection. These catalogs may facilitate future analysis of the functions of lncRNAs in innate immunity and related diseases.

Facile synthesis and electrochemical performances of hollow graphene spheres as anode material for lithium-ion batteries.

The hollow graphene oxide spheres have been successfully fabricated from graphene oxide nanosheets utilizing a water-in-oil emulsion technique, which were prepared from natural flake graphite by oxidation and ultrasonic treatment. The hollow graphene oxide spheres were reduced to hollow graphene spheres at 500°C for 3 h under an atmosphere of Ar(95%)/H2(5%). The first reversible specific capacity of the hollow graphene spheres was as high as 903 mAh g(-1) at a current density of 50 mAh g(-1). Even at a high current density of 500 mAh g(-1), the reversible specific capacity remained at 502 mAh g(-1). After 60 cycles, the reversible capacity was still kept at 652 mAh g(-1) at the current density of 50 mAh g(-1). These results indicate that the prepared hollow graphene spheres possess excellent electrochemical performances for lithium storage. The high rate performance of hollow graphene spheres thanks to the hollow structure, thin and porous shells consisting of graphene sheets. PACS: 81.05.ue; 61.48.Gh; 72.80.Vp.