Genetic diversity of norovirus associated with outbreaks in school children with acute gastroenteritis in Changzhou, China, 2018-2019.

Norovirus is one of the major causes of outbreaks and sporadic cases of acute gastroenteritis in school children. Obtaining local genotype diversity information regarding norovirus is important for developing and evaluating prevention strategies of the transmission of this virus in school children. Clinical specimens, obtained from the routine acute gastroenteritis surveillance network from 2018 to 2019, were primarily tested using commercial real-time PCR Kit. Samples with Ct value less than 25 were selected and used for complete genome sequencing and those with Ct value between 25 and 30 were selected and used for he partial VP1 and RdRp regions sequencing. Phylogenetic trees of the viral genome were constructed by using the neighbor-joining method with bootstrap analysis of 1000 replicates in MEGA 6.0. Epidemiological surveillance of acute intestinal infections (n = 384) showed high-level detection (73.18%) of human norovirus in school endemic acute gastroenteritis events in Changzhou, with obvious epidemic characteristics in autumn and winter. Through genotyping, it was found that 93.12% of norovirus were GII, including GII.2, GII.3, GII.4, GII.6, GII.7, and GII.17. By October 2019, two norovirus genotypes, GII.4[P31] and GII.17[P17], became the preponderant epidemic strains. Phylogenetic analysis of the new GII.17[P17] complete genomes showed close relationship with Miyagi strain identified in Japan in 2015, and GII.4[P31] showed close relationship with Jinan strain indentified in China in 2017. The study highlights the emerging role of GII.4[P31] and GII.17[P17] in causing endemic acute gastroenteritis outbreaks at school children, in Changzhou, China in 2019.

Re-utilization of Chinese medicinal herbal residue: waste wormwood rod-derived porous carbon as a low-cost adsorbent for methyl orange removal.

A cost-effective approach was applied to prepare porous carbon samples by the simple carbonization of wormwood rod followed by salt activator (NaCl) activation. The effect of preparation parameters on the characteristics of the wormwood rod-based porous carbons (WWRs) were studied. The properties of these samples were investigated by SEM, BET surface area, X-ray diffraction, FT-IR spectra and X-ray photoelectron spectrometer. The prepared WWRs were applied as new adsorbent materials to remove methyl orange (MO). The experimental results indicated that WWR-800 activated at 800 °C possesses the best adsorption performance. Several factors that affected the adsorption property of the system such as the solution pH, dosing of adsorbent, initial dye concentration and ionic strength were examined. In addition, the thermodynamic parameters and kinetic parameters of MO with WWR-800 were studied. The results indicated that the adsorption of MO on WWR-800 was an endothermic process and non-spontaneous under standard conditions. The maximum equilibrium adsorption capacity of MO on WWR-800 was 454.55 mg/g. After five adsorption/desorption cycles, the adsorption capacity of MO on WWR-800 remained at 94%, which indicated that wormwood rod-based porous carbon possessed good reusability.

Neonatal hand, foot, and mouth disease due to coxsackievirus A6 in Shanghai.

BACKGROUND: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. METHODS: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1ß, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. RESULTS: There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae. CONCLUSIONS: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

The coordinating role of the human norovirus minor capsid protein VP2 is essential to functional change and nuclear localization of the major capsid protein VP1.

Global outbreaks of norovirus (NOV) gastroenteritis are associated with the most prevalent genotype, GII.4. Mutations in the protruding domain 2 (P2 domain) of the norovirus major capsid protein (VP1) result in the emergence of various NOV variants, however, it is unclear whether the minor capsid protein (VP2) also affects the generation of VP1 variants. In this study, using a human 293T expression system, we investigated the interactions of VP1 and VP2 of three GII.4 strains, focusing on the changes in expression and cellular localization. We found that co-transfection with VP1 and VP2 leads to a significant increase in expression of both proteins compared to that in cells transfected with VP1 or VP2 alone. In contrast to VP1 expressed in the absence of VP2, which was dispersed throughout the cytosol, VP2 expressed in the absence of VP1 was found to be located in the nucleus. This could be attributed to a predicted specific nuclear localization signal found in this gene. When both proteins were expressed, VP1 was found together with VP2 in the nucleus. These results thus suggest that the VP2 of GII.4 NOVs affects the function and cellular location of VP1 and that, with the cooperation of VP2, VP1 could play a critical role in affecting cell functions by impairing the downstream transcriptional signaling and chromatin remodeling in the cell nuclei.

IFN-λ1 in CHO cells: its expression and biological activity.

BACKGROUND: Many studies have investigated the characteristics and biological activities of type III interferon (IFN), finding that it has similar features to type I IFN but also unique actions because it is recognized by a different receptor. RESULTS: A full-length recombinant human IFN-λ1 (rhIFN-λ1) cDNA was cloned into the pDF expression vector and stably expressed in Flp-In-CHO cells. After four purification steps (ammonium sulfate precipitation, SP Sepharose chromatography, Blue Sepharose 6 fast flow affinity chromatography and molecular sieve chromatography), the rhIFN-λ1 had a purity of about 90% and was found to have the predicted biological activities. The anti-viral activity of rhIFN-λ1 was determined as 106 IU/mg using the vesicular stomatitis virus (WISH-VSV) assay system. The anti-proliferation activity of rhIFN-λ1 was measured using the MTS method and the growth inhibition ratio was 57% higher than that for recombinant human IFN-α2b (rhIFN-α2b) when the rhIFN-λ1 concentration was 1000 IU/ml. rhIFN-λ1 had lower natural killer cell cytotoxicity than rhIFN-α2b. CONCLUSION: The Flp-In-CHO system is suitable for stably expressing rhIFN-λ1 that possesses the predicted anti-viral, anti-proliferation and natural killer cell cytotoxicity-promoting activities.

Comparison of interactions between human serum albumin and silver nanoparticles of different sizes using spectroscopic methods.

Three different sizes (15.9 ± 2.1 nm, 26.4 ± 3.2 nm and 39.8 ± 4.0 nm, respectively) of citrate-coated silver nanoparticles (SNPs) have been synthesized and characterized. The interactions of the synthesized SNPs with human serum albumin (HSA) at physiological pH have been systematically studied by UV-vis absorption spectroscopy, fluorescence spectroscopy, synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The results indicate that the SNPs can bind to HSA with high affinity and quench the intrinsic fluorescence of HSA. The binding constants and quenching rate constants were calculated. The apparent association constants (Kapp ) values are 2.14 × 10(4) M(-1) for 15.9 nm SNP, 1.65 × 10(4) M(-1) for 26.4 nm SNP and 1.37 × 10(4) M(-1) for 39.8 nm SNP, respectively. The values of binding constant obtained from the fluorescence quenching data match well with that determined from the absorption spectral changes. These results suggest that the smaller SNPs have stronger interactions to HSA than the larger ones at the same concentrations. Synchronous fluorescence, three-dimensional fluorescence and CD spectroscopy studies show that the synthesized SNPs can induce slight conformational changes in HSA.

Biological pretreatment with white rot fungi for preparing hierarchical porous carbon from Banlangen residues with high performance for supercapacitors and dye adsorption.

White rot fungi possess superior infiltrability and biodegradability on lignocellulosic substrates, allowing them to form tailored microstructures which are conducive to efficient carbonization and chemical activation. The present research employed white rot fungus pretreatment as a viable approach for preparing porous carbon from Banlangen residues. The resultant F-A-BLGR-PC prepared by pretreating Banlangen residues with white rot fungi followed by carbonization and activation has a hierarchical porous structure with a high specific surface area of 898 m2 g-1, which is 43.4% greater than that of the unprocessed sample (R-BLGR-PC). When used as an electrode for supercapacitors, the F-A-BLGR-PC demonstrated a high specific capacitance of 308 F g-1 at 0.5 A g-1 in 6 M KOH electrolyte in three-electrode configuration. Moreover, the F-A-BLGR-PC based symmetric supercapacitor device achieved a superb cyclic stability with no obvious capacitance decay after 20,000 cycles at 5 A g-1 in 1 M Na2SO4 electrolyte. Additionally, the F-A-BLGR-PC sample was found to be an ideal adsorbent for removing methyl orange (MO) from water, exhibiting an adsorption ability of 173.4 mg g-1 and a maximum removal rate of 86.6%. This study offers a promising method for the preparation of a porous carbon with a high specific surface area in a biological way using white rot fungi pretreatment, and the derived carbon can not only be applied in energy storage but also in environmental remediation, catalysis, and so on.

Safe pseudovirus-based assay for neutralization antibodies against influenza A(H7N9) virus.

Serologic studies are urgently needed to assist in understanding an outbreak of influenza A(H7N9) virus. However, a biosafety level 3 laboratory is required for conventional serologic assays with live lethal virus. We describe a safe pseudovirus-based neutralization assay with preliminary assessment using subtype H7N9-infected samples and controls.

Rotavirus infection and its genetic characterization in non-hospitalized adults with acute gastroenteritis in Shanghai, China.

Rotavirus is a major cause of acute gastroenteritis in infants and young children, while its role as a pathogen in adults has long been underappreciated. In order to describe the epidemiological patterns and genetic characteristics of rotavirus causing sporadic acute gastroenteritis in adults, hospital-based surveillance of rotavirus infections was conducted in Shanghai, China, between June 2010 and May 2011. Stool specimens were collected from outpatients with acute gastroenteritis admitted to three local hospitals. Rotavirus was detected using a colloidal gold test device. G and P genotyping were performed by multiplex PCR assays, and the VP7 gene of G9 strains were sequenced for further genetic characterization. Of 1,479 adult diarrheal stool samples examined during the 1-year surveillance period, 138 (9.3 %) were found to be rotavirus positive. G1 appeared to be the predominant genotype (35.5 %), suggesting a shift from genotype G3 to G1 in the study population in Shanghai. Meanwhile, a high frequency of genotype G9 (27.5 %) was also observed, and G9 was also predominant (38.1 %) in the small number of children (n=123) involved in the present study. Other specificities detected in adults were G2 (12.3 %) and G3 (13.8 %). For P genotyping, only two types, P[8] and P[4], were detected. P[8] was dominant in both children and adults. Sequence and phylogenetic analysis revealed that these strains could be divided into two different groups, with clustering within G9 lineage 3 and the subcluster of Japanese and Chinese G9 strains, respectively. In comparison to the previous data, G9 strains established themselves in a short time span as an important genotype in Shanghai, China.

Synergetic Photodynamic-Photothermal-Chemotherapy Dual Targeting Nanoplatform Effective Against Breast Cancer in-Mice Model.

Introduction: Combined multimodal therapy for breast cancer is a promising therapeutic approach to increase treatment efficacy and reduce systemic toxicity. The present study aimed to develop a novel multifunctional drug release nanoplatform based on RGD-conjugated hyaluronic acid (HA)-functionalized copper sulfide (CuS) for activatable dual-targeted synergetic therapy against cancer. Methods: The pH and NIR-responsive dual-targeting nanoplatform CuS:Ce6@HA:DOX@RGD was prepared, characterized, and evaluated for its stability and photodynamic and photothermal properties. The loading and release of the drug were measured at different pH values with or without laser radiation using the dialysis method. The cellular uptake of the platform specifically by the tumor cells treated with different formulations was investigated through fluorescence imaging. The in vitro and in vivo biosafety levels were assessed systematically. Finally, the antitumor efficiencies against breast cancer were assessed via in vitro and in vivo experiments. Results: The spheroid CuS:Ce6@HA:DOX@RGD exhibited remarkable stability and monodispersity in solution. The photosensitive CuS and Ce6 could simultaneously absorb the near-infrared light efficiently to convert NIR light to fatal heat and to generate reactive oxygen species. The CuS:Ce6@HA:DOX@RGD dissociated under an acid environment, causing the release of DOX into the tumor to accelerate upon laser irradiation. The CuS:Ce6@HA:DOX@RGD exhibited target-specific and strong binding ability via a synergic CD44/αvß3 receptor-mediated bimodal targeting, which led to improved therapeutic efficacy. The tumor growth was effectively inhibited using synergetic photodynamic/photothermal/chemo therapy. No evident systemic toxicity was noted during treatment. Conclusion: The newly prepared CuS:Ce6@HA:DOX@RGD has great potential as an activatable theranostic nanoplatform for efficient dual-targeted synergistic therapy against breast cancer.

Next-Generation Rapid and Ultrasensitive Lateral Flow Immunoassay for Detection of SARS-CoV-2 Variants.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for rapid and accurate viral detection at the point-of-care testing (POCT). Compared with nucleic acid detection, lateral flow immunoassay (LFIA) is a rapid and flexible method for POCT detection. However, the sensitivity of LFIA limits its use for early identification of patients with COVID-19. Here, an innovative surface-enhanced Raman scattering (SERS)-LFIA platform based on two-dimensional black phosphorus decorated with Ag nanoparticles as important antigen-capturing and Raman-signal-amplification unit was developed for detection of SARS-CoV-2 variants within 5-20 min. The novel SERS-LFIA platform realized a limit of detection of 0.5 pg/mL and 100 copies/mL for N protein and SARS-CoV-2, demonstrating 1000 times more sensitivity than the commercial LFIA strips. It could reliably detect seven different SARS-CoV-2 variants with cycle threshold (Ct) < 38, with sensitivity and specificity of 97 and 100%, respectively, exhibiting the same sensitivity with q-PCR. Furthermore, the detection results for 48 SARS-CoV-2-positive nasopharyngeal swabs (Ct = 19.8-38.95) and 96 negative nasopharyngeal swabs proved the reliability of the strips in clinical application. The method also had good specificity in double-blind experiments involving several other coronaviruses, respiratory viruses, and respiratory medications. The results showed that the innovative SERS-LFIA platform is expected to be the next-generation antigen detection technology. The inexpensive amplification-free assay combines the advantages of rapid low-cost POCT and highly sensitive nucleic acid detection, and it is suitable for rapid detection of SARS-CoV-2 variants and other pathogens. Thus, it could replace existing antigens and nucleic acids to some extent.

Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

BACKGROUND: A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. METHODS: We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. RESULTS: One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. CONCLUSIONS: Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

Evaluation of Biological Pretreatment of Wormwood Rod Reies with White Rot Fungi for Preparation of Porous Carbon.

In this work, the wormwood rod residues are pretreated with white rot fungi as the precursor to preparing porous carbon following a simple carbonization and activation process (denoted herein as FWRA sample). The FWRA sample possesses abundant hierarchical pores structure with high specific surface area (1165.7 m2 g-1) and large pore volume (1.02 cm3 g-1). As an electrode for supercapacitors, the FWRA sample offers a high specific capacitance of 443.2 F g-1 at 0.5 A g-1 and superb rate ability holding a specific capacitance of 270 F g-1 at 100 A g-1 in 6 M KOH electrolyte. The corresponding symmetrical capacitor has a superb cyclic stability with a low specific capacitance decay rate of 0.4% after 20,000 cycles at 5 A g-1 in 1 M Na2SO4 electrolyte. Moreover, measurements revealed that when used as adsorbent, the FWRA sample is ideal for removing methyl orange (MO) from water, exhibiting a superior adsorption ability of 260.8 mg g-1. Therefore, this study is expected to provide a simple and environmentally friendly technique for the generation of value-added and functional porous carbon materials from Chinese medicinal herbal residues, thus offering promising candidates for broad application areas.

Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai, China, 2016-2020.

Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%-100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.

A triclinic polymorph with Z = 3 of N,N'-bis-(2-pyrid-yl)oxamide.

The asymmetric unit of the title compound, C(12)H(10)N(4)O(2), contains three half-mol-ecules. Each half-mol-ecule is completed by crystallographic inversion symmetry. The title compound, (I), is a polymorph of the structure, (II), reported by Hsu & Chen [Eur. J. Inorg. Chem. (2004), 1488-1493]. In the original report, the compound crystallized in the tetra-gonal space group P[Formula: see text]2(1)c (Z = 8), whereas the structure reported here is triclinic (P[Formula: see text], Z = 3). In both forms, each oxamide mol-ecule is almost planar (with maximum deviations are 0.266 and 0.166 Å) and the O atoms are trans oriented. The principal difference between the two forms lies in the different hydrogen-bonding patterns. In (I), two N-H⋯O and one N-H⋯N hydrogen bonds link the mol-ecules, forming a two-dimensional network, whereas in (II) there are no classical hydrogen bonds to O atoms and only weak C-H⋯O inter-actions are found along with rings of N-H⋯N bonds.

Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication.

Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus (H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial (A549) cells. In detail, the expression of hexokinase 2 (HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells, and the expression of pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase kinase 3 (PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1 (HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.

A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.

Astragaloside IV attenuates IL-1ß secretion by enhancing autophagy in H1N1 infection.

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1ß) and pro-IL-1ß protein level, but significantly decreased secretion of IL-1ß, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1ß in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1ß secretion.

The activation of antiviral RNA interference not only exists in neural progenitor cells but also in somatic cells in mammals.

The RNA interference (RNAi) pathway directs an important antiviral immunity mechanism in plants and invertebrates. Recently, we and others have demonstrated that the antiviral RNAi response is also conserved in mammals, at least to five distinct RNA viruses, including Zika virus (ZIKV). ZIKV may preferentially infect neuronal progenitor cells (NPCs) in the developing foetal brain. Ex vivo ZIKV infection induces RNAi-mediated antiviral response in human NPCs, but not in the more differentiated NPCs or somatic cells. However, litter is known about the in vivo property or function of the virus-derived small-interfering RNAs (vsiRNAs) targeting ZIKV. Here we report a surprising observation: different from ex vivo observations, viral small RNAs (vsRNAs) targeting ZIKV were produced in vivo upon infection in both central neuron system (CNS) and muscle tissues. In addition, our findings demonstrate the production of canonical vsiRNAs in murine CNS upon antiviral RNAi activation by Sindbis virus (SINV), suggesting the possibility of antiviral immune strategy applied by mammals in the CNS.