Hepatitis B virus RNAs co-opt ELAVL1 for stabilization and CRM1-dependent nuclear export.

Hepatitis B virus (HBV) chronically infects 296 million people worldwide, posing a major global health threat. Export of HBV RNAs from the nucleus to the cytoplasm is indispensable for viral protein translation and genome replication, however the mechanisms regulating this critical process remain largely elusive. Here, we identify a key host factor embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) that binds HBV RNAs and controls their nuclear export. Using an unbiased quantitative proteomics screen, we demonstrate direct binding of ELAVL1 to the HBV pregenomic RNA (pgRNA). ELAVL1 knockdown inhibits HBV RNAs posttranscriptional regulation and suppresses viral replication. Further mechanistic studies reveal ELAVL1 recruits the nuclear export receptor CRM1 through ANP32A and ANP32B to transport HBV RNAs to the cytoplasm via specific AU-rich elements, which can be targeted by a compound CMLD-2. Moreover, ELAVL1 protects HBV RNAs from DIS3+RRP6+ RNA exosome mediated nuclear RNA degradation. Notably, we find HBV core protein is dispensable for HBV RNA-CRM1 interaction and nuclear export. Our results unveil ELAVL1 as a crucial host factor that regulates HBV RNAs stability and trafficking. By orchestrating viral RNA nuclear export, ELAVL1 is indispensable for the HBV life cycle. Our study highlights a virus-host interaction that may be exploited as a new therapeutic target against chronic hepatitis B.

Enhancing the mechanical performance of poly(ether ether ketone)/zinc oxide nanocomposites to provide promising biomaterials for trauma and orthopedic implants.

Poly(ether ether ketone)/zinc oxide (PEEK/ZnO) composites were manufactured by using the injection molding technique. Before blending with the PEEK resin matrix, some ZnO nanoparticles were modified by γ-aminopropyltriethoxylsilane (APTES). The effect of surface modification of ZnO nanoparticles by amino groups and Si-O bonds was investigated. PEEK/ZnO composites were characterized by scanning electron microscopy (SEM), thermogravimetric analysis, and X-ray diffraction. The scanning electron micrographs showed that ZnO nanoparticles were encapsulated in the PEEK phase; within this phase, the nanoparticles were homogeneously dispersed. Mechanical and tribological properties were measured by tensile strength, flexural strength, coefficient of friction, and wear rate. It was shown that the interfacial compatibility between ZnO nanoparticles and PEEK matrix was significantly enhanced due to the amino and Si-O bonds decorated on the ZnO nanoparticles. More importantly, the thermal stability of PEEK improved upon the incorporation of ZnO nanoparticles into this matrix. Cell viability studies with mouse osteoblasts demonstrated that cell growth on PEEK and PEEK/ZnO was significantly enhanced. On the basis of the obtained results, PEEK/ZnO composites are recommended as promising candidates for orthopaedic materials and trauma implants.