The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription.

Zika virus (ZIKV) targets the neural progenitor cells (NPCs) in brain during intrauterine infections and consequently causes severe neurological disorders, such as microcephaly in neonates. Although replicating in the cytoplasm, ZIKV dysregulates the expression of thousands of host genes, yet the detailed mechanism remains elusive. Herein, we report that ZIKV encodes a unique DNA-binding protein to regulate host gene transcription in the nucleus. We found that ZIKV NS5, the viral RNA polymerase, associates tightly with host chromatin DNA through its methyltransferase domain and this interaction could be specifically blocked by GTP. Further study showed that expression of ZIKV NS5 in human NPCs markedly suppressed the transcription of its target genes, especially the genes involved in neurogenesis. Mechanistically, ZIKV NS5 binds onto the gene body of its target genes and then blocks their transcriptional elongation. The utero electroporation in pregnant mice showed that NS5 expression significantly disrupts the neurogenesis by reducing the number of Sox2- and Tbr2-positive cells in the fetal cortex. Together, our findings demonstrate a molecular clue linking to the abnormal neurodevelopment caused by ZIKV infection and also provide intriguing insights into the interaction between the host cell and the pathogenic RNA virus, where the cytoplasmic RNA virus encodes a DNA-binding protein to control the transcription of host cell in the nuclei.

Accelerated Catalytic Ozonation in a Mesoporous Carbon-Supported Atomic Fe-N4 Sites Nanoreactor: Confinement Effect and Resistance to Poisoning.

The design of a micro-/nanoreactor is of great significance for catalytic ozonation, which can achieve effective mass transfer and expose powerful reaction species. Herein, the mesoporous carbon with atomic Fe-N4 sites embedded in the ordered carbon nanochannels (Fe-N4/CMK-3) was synthesized by the hard-template method. Fe-N4/CMK-3 can be employed as nanoreactors with preferred electronic and geometric catalytic microenvironments for the internal catalytic ozonation of CH3SH. During the CH3SH oxidation process, the mass transfer coefficient of the Fe-N4/CMK-3 confined system with sufficient O3 transfer featured a level of at least 1.87 × 10-5, which is 34.6 times that of the Fe-N4/C-Si unconfined system. Detailed experimental studies and theoretical calculations demonstrated that the anchored atomic Fe-N4 sites and nanoconfinement effects regulated the local electronic structure of the catalyst and promoted the activation of O3 molecules to produce atomic oxygen species (AOS) and reactive oxygen species (ROS), eventually achieving efficient oxidation of CH3SH into CO2/SO42-. Benefiting from the high diffusion rate and the augmentation of AOS/ROS, Fe-N4/CMK-3 exhibited an excellent poisoning tolerance, along with high catalytic durability. This contribution provides the proof-of-concept strategy for accelerating catalytic ozonation of sulfur-containing volatile organic compounds (VOCs) by combining confined catalysis and atomic catalysts and can be extended to the purification of other gaseous pollutants.

Efficient catalytic activity and bromate minimization over lattice oxygen-rich MnOOH nanorods in catalytic ozonation of bromide-containing organic pollutants: Lattice oxygen-directed redox cycle and bromate reduction.

The inhibition of bromate formation is a challenge for the application of ozonation in water treatment due to the carcinogenicity and nephrotoxicity of bromate. In this study, the high-mobility lattice oxygen-rich MnOOH nanorods were synthesized successfully and applied for the bromate inhibition during catalytic ozonation in bromide and organic pollutants-containing wastewater treatment. The catalytic ozonation system using lattice oxygen-rich MnOOH nanorods exhibited an excellent performance in bromate control with an inhibition efficiency of 54.1% compared with the sole ozonation process. Furthermore, with the coexistence of 4-nitrophenol, the catalytic ozonation process using lattice oxygen-rich MnOOH nanorods could inhibit the bromate formation and boost the degradation of 4-nitrophenol simultaneously. Based on the experiments of ozone decomposition, surface manganese inactivation and reactive oxygen species detection, the inhibition of bromate could be attributed to the effective decomposition of ozone with generating more ·O2- and the reduction of bromate into bromide by lattice oxygen-rich MnOOH. The existed surface Mn(IV) on lattice oxygen-rich MnOOH can accept electrons from lattice oxygen and ·O2- to generate surface transient Mn(II)/Mn(III), in which Mn(II)/Mn(III) can promote the reduction of bromate into bromide during catalytic ozonation. This study provides a promising strategy for the development of bromate-controlling technologies in water treatment.

Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells.

Nucleic acid-based systems play important roles in antiviral defense, including CRISPR/Cas that adopts RNA-guided DNA cleavage to prevent DNA phage infection and RNA interference (RNAi) that employs RNA-guided RNA cleavage to defend against RNA virus infection. Here, we report a novel type of nucleic acid-based antiviral system that exists in mouse embryonic stem cells (mESCs), which suppresses RNA virus infection by DNA-mediated RNA cleavage. We found that the viral RNA of encephalomyocarditis virus can be reverse transcribed into complementary DNA (vcDNA) by the reverse transcriptase (RTase) encoded by endogenous retrovirus-like elements in mESCs. The vcDNA is negative-sense single-stranded and forms DNA/RNA hybrid with viral RNA. The viral RNA in the heteroduplex is subsequently destroyed by cellular RNase H1, leading to robust suppression of viral growth. Furthermore, either inhibition of the RTase activity or depletion of endogenous RNase H1 results in the promotion of virus proliferation. Altogether, our results provide intriguing insights into the antiviral mechanism of mESCs and the antiviral function of endogenized retroviruses and cellular RNase H. Such a natural nucleic acid-based antiviral mechanism in mESCs is referred to as ERASE (endogenous RTase/RNase H-mediated antiviral system), which is an addition to the previously known nucleic acid-based antiviral mechanisms including CRISPR/Cas in bacteria and RNAi in plants and invertebrates.