Neuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes.

Herpes simplex virus 1 (HSV-1) latent infection entails repression of viral lytic genes in neurons. By functional screening using luciferase-expressing HSV-1, we identify ten neuron-specific microRNAs potentially repressing HSV-1 neuronal replication. Transfection of miR-9, the most active candidate from the screen, decreases HSV-1 replication and gene expression in Neuro-2a cells. Ectopic expression of miR-9 from lentivirus or recombinant HSV-1 suppresses HSV-1 replication in male primary mouse neurons in culture and mouse trigeminal ganglia in vivo, and reactivation from latency in the primary neurons. Target prediction and validation identify transcription factors Oct-1, a known co-activator of HSV transcription, and all three Onecut family members as miR-9 targets. Knockdown of ONECUT2 decreases HSV-1 yields in Neuro-2a cells. Overexpression of each ONECUT protein increases HSV-1 replication in Neuro-2a cells, human induced pluripotent stem cell-derived neurons, and primary mouse neurons, and accelerates reactivation from latency in the mouse neurons. Mutagenesis, ChIP-seq, RNA-seq, ChIP-qPCR and ATAC-seq results suggest that ONECUT2 can nonspecifically bind to viral genes via its CUT domain, globally stimulate viral gene transcription, reduce viral heterochromatin and enhance the accessibility of viral chromatin. Thus, neuronal miR-9 promotes viral epigenetic silencing and latency by targeting multiple host transcription factors important for lytic gene activation.

Superior Enhancement of the UHMWPE Fiber/Epoxy Interface through the Combination of Plasma Treatment and Polypyrrole In-Situ Grown Fibers.

Obtaining a robust fiber/matrix interface is crucial for enhancing the mechanical performance of fiber-reinforced composites. This study addresses the issue by presenting a novel physical-chemical modification method to improve the interfacial property of an ultra-high molecular weight polyethylene (UHMWPE) fiber and epoxy resin. The UHMWPE fiber was successfully grafted with polypyrrole (PPy) for the first time after a plasma treatment in an atmosphere of mixed oxygen and nitrogen. The results demonstrated that the maximum value of the interfacial shear strength (IFSS) of the UHMWPE fiber/epoxy reached 15.75 MPa, which was significantly enhanced by 357% compared to the pristine UHMWPE fiber. Meanwhile, the tensile strength of the UHMWPE fiber was only slightly reduced by 7.3%, which was furtherly verified by the Weibull distribution analysis. The surface morphology and structure of the PPy in-situ grown UHMWPE fibers were studied using SEM, FTIR, and contact angle measurement. The results showed that the enhancement of the interfacial performance was attributed to the increased fiber surface roughness and in-situ grown groups, which improved the surface wettability between the UHMWPE fibers and epoxy resins.