Publications by authors named "Yuan Zhan"

49 Publications

p55PIK Deficiency and its N-terminal Derivative inhibit Inflammation and Emphysema in COPD mouse model.

Am J Physiol Lung Cell Mol Physiol 2021 May 5. Epub 2021 May 5.

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Background: Chronic obstructive pulmonary disease (COPD) is comprised of chronic inflammation and emphysema. Recent studies show that Class IA phosphatidylinositol 3-kinases (PI3Ks) play an important role in the regulation of inflammation and emphysema. However, there are few studies on their regulatory subunits. p55PIK is a regulatory subunit of Class IA PI3Ks and its unique N-terminal gives it special functions.

Methods: p55PIK expression in the lungs of nonsmokers, smokers, and COPD patients were examined. We established a fusion protein TAT-N15 from the N-terminal effector sequence of p55PIK and TAT (the transduction domain of HIV trans-activator protein), and investigated the effects of silencing p55PIK or adding TAT-N15 on cigarette smoke exposure at the cellular and animal level.

Results: p55PIK expression was increased in COPD patients. p55PIK deficiency and TAT-N15 significantly inhibited the cigarette smoke extract-induced IL-6, IL-8, and activation of the Akt and the NF-κB pathway in BEAS-2B. p55PIK deficiency and TAT-N15 intranasal administration prevented emphysema and the lung function decline in mice exposed to smoke for 6 months. p55PIK deficiency and TAT-N15 significantly inhibited lung inflammatory infiltration, reduced levels of IL-6, KC in mice lung homogenate, and inhibited activation of the Akt and the NF-κB signaling in COPD mice lungs.

Conclusion: Our studies indicate that p55PIK is involved in the pathogenesis of COPD, and its N-terminal derivative TAT-N15 could be an effective drug in the treatment of COPD by inhibiting the activation of the Akt and the NF-κB pathway.
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http://dx.doi.org/10.1152/ajplung.00560.2020DOI Listing
May 2021

Hybrid double-network hydrogel for highly stretchable, excellent sensitive, stabilized, and transparent strain sensors.

J Biomater Sci Polym Ed 2021 Apr 26:1-14. Epub 2021 Apr 26.

Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials (Hubei University), College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China.

Nowadays, great effort has been devoted to fabricate flexible wearable sensor with high stretchability, moderate modulus, favorable durability, excellent transparency, and satisfactory sensitivity. In this work, we report the preparation of a hybrid double-network (DN) hydrogel by a simple one-pot method. First, chitosan was added into an AlCl solution to form Al-chitosan complex (CS-Al). Second, the hybrid CS/Al-poly(acrylamide) (PAM) double-network (DN) hydrogels were constructed in-situ polymerization of acrylamide (AM) in present of Al-chitosan complex. Thanks to the existence of electrically conductive CS-Al networks, the resulting hybrid DN hydrogel exhibits excellent stretchability, fatigue resistance, transparency, and conductivity. Furthermore, the CS/Al-PAM DN hydrogel could be used as strain sensor, and demonstrates many desired virtues, including satisfactory sensitivity (gauge factors of 1.7 to 12.1), wide detection range (up to 1500%), low limit of discernment (1% strain), high reliability, and excellent durability (1000 cycles). More significantly, the manufactured hydrogel-based strain sensor can be employed as wearable devices to precisely detect various human movements.
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http://dx.doi.org/10.1080/09205063.2021.1922170DOI Listing
April 2021

Identify Candidate Genes in the Interaction between Abdominal Aortic Aneurysm and Type 2 Diabetes Mellitus by Using Biomedical Discovery Support System.

Chin Med Sci J 2021 Mar;36(1):50-56

Department of Vascular Surgery, Tian Jin First Center Hospital, Tianjin 300192, China.

Objective To explore the candidate genes that play significant roles in the interconnection between abdominal aortic aneurysm (AAA) and type 2 diabetes mellitus (DM). Methods We used the Biomedical Discovery Support System (BITOLA) to screen out the candidate intermediate molecular (CIM) "Gene or Gene Product" that are related to AAA and DM. The dataset of GSE13760, GSE7084, GSE57691, GSE47472 were used to analyze the differentially expressed genes (DEGs) of AAA and DM compared to the healthy status. We used the online tool of Venny 2.1 assisted by manual checking to identify the overlapped DEGs with the CIMs. The Human eFP Browser was applied to examine the tissue specific expression levels of the detected genes in order to recognize strong expressed genes in both human artery and pancreatic tissue. Results There were 86 CIMs suggested by the closed BITOLA system. Among all the DEGs of AAA and DM, 8 genes in GSE7084 (ISG20, ITGAX, DSTN, CCL5, CCR5, AGTR1, CD19, CD44) and 2 genes in GSE13760 (PSMD12, FAS) were found to be overlapped with the 86 CIMs. By manual checking and comparing with tissue-specific gene data through Human eFP Browser, the gene PSMD12 (proteasome 26S subunit, non-ATPase 12) was recognized to be strongly expressed in both the aorta and pancreatic tissue. Conclusion We proposed a hypothesis through text mining that PSMD12 might be involved or potentially involved in the interconnection between AAA and DM, which may provide a new clue for studies on novel therapeutic strategies for the two diseases.
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http://dx.doi.org/10.24920/003711DOI Listing
March 2021

Efficacy of corticosteroid in patients with COVID-19: A multi-center retrospective study and meta-analysis.

J Med Virol 2021 Mar 5. Epub 2021 Mar 5.

Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

To evaluate the efficacy of corticosteroids on coronavirus disease 2019 (COVID-19) patients with different levels of disease severity. In our multicenter study, 543 patients with confirmed COVID-19 were classified as non-severe group and severe group, and then were compared respectively for all-cause mortality and length of hospital stay between those who received corticosteroids and not. By searching in PubMed, Web of Science, Embase, and CNKI, we identified 13 retrospective studies and 6 random control trials eligible for criteria of inclusion, and conducted comprehensive meta-analyses assessing the impacts of corticosteroids on mortality, length of stay, duration of RNA clearance and duration of fever. Our multicenter study demonstrated that low-dose corticosteroids can reduce mortality in the multivariable Cox regression analysis for severe patients (p = .03), while presented no influence in univariable analysis for non-severe patients (p = .14). From multivariable analyses, patients with corticosteroids in non-severe group had longer duration of hospitalization (p = .003), but did not in severe group (p = .18). Moreover, for severe patients, corticosteroids can evidently shorten duration of fever. The same results were summarized in the meta-analyses supplemented with the result that corticosteroids delayed viral clearing in non-severe patients. Corticosteroids should be considered based on patient's condition. For patients with non-severe COVID-19, corticosteroid was not recommended as a routine therapeutic initiative as that presented prolonged duration of hospitalization and delayed viral clearing, as well as no positive impact on prognosis. While low-dose corticosteroids may benefit patients with severe COVID-19 for it can manifestly lower risk of death and improve the clinical status to some extent.
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http://dx.doi.org/10.1002/jmv.26914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014848PMC
March 2021

Silent information regulator type-1 mediates amelioration of inflammatory response and oxidative stress in lipopolysaccharide-induced acute respiratory distress syndrome.

J Biochem 2021 Jan 22. Epub 2021 Jan 22.

Department of Intensive Care Unit, the Second People's Hospital of Hefei, No. 246 Heping Road, Yaohai District, Hefei 230011, Anhui, China.

Silent information regulator type-1 (SIRT1) is crucial during the development of acute respiratory distress syndrome (ARDS). We aimed to explore whether SIRT1 activation could protect against ARDS. SIRT1 was activated by its agonist SRT1720. ARDS was induced by intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS). Lung injuries were determined by the lung wet/dry ratio, inflammatory cells in the broncho-alveolar lavage fluid (BALF) and histological analysis. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay. The accumulation of neutrophils was detected by myeloperoxidase activity. Oxidative stress was evaluated by malondialdehyde, reduced glutathione, superoxide dismutaseand catalase activities. The protein expression levels were detected using Western blot. SIRT1 activation, either by SRT1720 administration or recombinant SIRT1 expression eliminated high dose LPS-induced mortality in mice, attenuated lung injury, influenced cytokine release in BALF, and decreased oxidative stress in the lung tissues of ARDS mice. Mechanically, SRT1720 administration inhibited p65 phosphorylation in the lung tissues of ARDS mice. SIRT1 ameliorates inflammatory response and oxidative stress in LPS-induced ARDS.
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http://dx.doi.org/10.1093/jb/mvaa150DOI Listing
January 2021

Deterministic Generation of Loss-Tolerant Photonic Cluster States with a Single Quantum Emitter.

Authors:
Yuan Zhan Shuo Sun

Phys Rev Lett 2020 Nov;125(22):223601

JILA and Department of Physics, University of Colorado, Boulder, Colorado 80309, USA.

A photonic cluster state with a tree-type entanglement structure constitutes an efficient resource for quantum error correction of photon loss. But the generation of a tree cluster state with an arbitrary size is notoriously difficult. Here, we propose a protocol to deterministically generate photonic tree states of arbitrary size by using only a single quantum emitter. Photonic entanglement is established through both emission and rescattering from the same emitter, enabling fast and resource-efficient entanglement generation. The same protocol can also be extended to generate more general tree-type entangled states.
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http://dx.doi.org/10.1103/PhysRevLett.125.223601DOI Listing
November 2020

Newcastle Disease virus infection activates PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways to benefit viral mRNA translation via interaction of the viral NP protein and host eIF4E.

PLoS Pathog 2020 06 30;16(6):e1008610. Epub 2020 Jun 30.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, P.R. China.

Newcastle disease virus (NDV), a member of the Paramyxoviridae family, can activate PKR/eIF2α signaling cascade to shutoff host and facilitate viral mRNA translation during infection, however, the mechanism remains unclear. In this study, we revealed that NDV infection up-regulated host cap-dependent translation machinery by activating PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways. In addition, NDV infection induced p38 MAPK/Mnk1 signaling participated 4E-BP1 hyperphosphorylation for efficient viral protein synthesis when mTOR signaling is inhibited. Furthermore, NDV NP protein was found to be important for selective cap-dependent translation of viral mRNAs through binding to eIF4E during NDV infection. Taken together, NDV infection activated multiple signaling pathways for selective viral protein synthesis in infected cells, via interaction between viral NP protein and host translation machinery. Our results may help to design novel targets for therapeutic intervention against NDV infection and to understand the NDV anti-oncolytic mechanism.
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http://dx.doi.org/10.1371/journal.ppat.1008610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326156PMC
June 2020

Electron transfer pathways and kinetic analysis of cathodic simultaneous nitrification and denitrification process in microbial fuel cell system.

Environ Res 2020 07 14;186:109505. Epub 2020 Apr 14.

Department of Environmental Science and Engineering, School of Energy and Environment, Southeast University, Nanjing, Jiangsu, 210096, China; Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Southeast University, Nanjing, Jiangsu, 210009, China. Electronic address:

Microbial fuel cell (MFC) is an innovative bioconversion technology for wastewater treatment accompanied with electricity recovery. In this study, a kinetic model was developed base on Activated Sludge Model No.1 (ASM1) to describe electron transfer pathways during the simultaneous nitrification and denitrification (SND) process in the biocathode system of a dual-chamber MFC. The batch running of the dual-chamber MFC system showed that it produced a power density up to 2.96 W m within 48 h, the achieved SND efficiency and autotrophic denitrification ratio in the cathodic denitrification process were up to 87.3 ± 0.8% and 69.5 ± 6.6%, respectively. Meanwhile, by integrating nitrification, autotrophic denitrification, heterotrophic denitrification, organic carbon oxidation, and oxygen reduction in the cathode, the model was able to precisely fit the concentration variations of NH-N, dissolved oxygen (DO) and chemical oxygen demand (COD) during the cathodic SND process (R ≥ 0.9876). The cathode electrons tended to be completely utilized with the increase of autotrophic denitrification ratio in the cathodic denitrification process. When the nitrification rate was enhanced, the autotrophic denitrification would prevail in the competition with the heterotrophic denitrification. In summary, the developed model was confirmed to be effective and reliable for describing the electron transfer pathways and predicting the performance of the nitrogen removal reactions during the cathodic SND process in a double-chamber MFC.
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http://dx.doi.org/10.1016/j.envres.2020.109505DOI Listing
July 2020

Priming With the Green Leaf Volatile (Z)-3-Hexeny-1-yl Acetate Enhances Salinity Stress Tolerance in Peanut ( L.) Seedlings.

Front Plant Sci 2019 20;10:785. Epub 2019 Jun 20.

Shandong Provincial Key Laboratory of Dryland Farming Technology, College of Agronomy, Qingdao Agricultural University, Qingdao, China.

Green leaf volatiles play vital roles in plant biotic stress; however, their functions in plant responses to abiotic stress have not been determined. The aim of this study was to investigate the possible role of (Z)-3-hexeny-1-yl acetate (Z-3-HAC), a kind of green leaf volatile, in alleviating the salinity stress of peanut () seedlings and the underlying physiological mechanisms governing this effect. One salt-sensitive and one salt-tolerant peanut genotype were primed with 200 μM Z-3-HAC at the 4-week-old stage before they were exposed to salinity stress. Physiological measurements showed that the primed seedlings possessed higher relative water content, net photosynthetic rate, maximal photochemical efficiency of photosystem II, activities of the antioxidant enzymes, and osmolyte accumulation under salinity conditions. Furthermore, the reactive oxygen species, electrolyte leakage, and malondialdehyde content in the third fully expanded leaves were significantly lower than in nonprimed plants. Additionally, we found that application of Z-3-HAC increased the total length, surface area, and volume of the peanut roots under salinity stress. These results indicated that the green leaf volatile Z-3-HAC protects peanut seedlings against damage from salinity stress through priming for modifications of photosynthetic apparatus, antioxidant systems, osmoregulation, and root morphology.
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http://dx.doi.org/10.3389/fpls.2019.00785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621544PMC
June 2019

Enantioselective determination of ketamine in dog plasma by chiral liquid chromatography-tandem mass spectrometry.

Biomed Chromatogr 2019 Sep 2;33(9):e4578. Epub 2019 Jun 2.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Ketamine is an N-methyl-d-aspartate receptor antagonist that is usually used clinically as a racemic mixture. Its two enantiomers exhibit different pharmacological activities. To determine whether the enantiomers have different pharmacokinetic profiles, a chiral liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of ketamine enantiomers in dog plasma. The enantiomers of ketamine were extracted from 50 μL of plasma by methyl tert-butyl ether. Adequate chromatographic retention and baseline resolution of the enantiomers were achieved within a runtime of 5 min on a chiral column coated with polysaccharide derivatives, using a gradient mobile phase of acetonitrile and 10 mm ammonium bicarbonate aqueous solution. Ketamine enantiomers were detected by mass spectrometry with multiple reaction monitoring mode using the transitions of m/z 238.3 → 125.9 for the analytes and m/z 237.1 → 194.1 for carbamazepine (internal standard). The method was linear over the concentration range from 0.5 to 500 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was 0.5 ng/mL. The intra- and inter-day precision was <7.3% and 8.5% for R- and S-ketamine, respectively. The accuracy was 92.9-110.4% for R-ketamine and 99.8-102.4% for S-ketamine. The method was successfully applied to characterize the stereoselective pharmacokinetic profiles of ketamine in beagle dogs.
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http://dx.doi.org/10.1002/bmc.4578DOI Listing
September 2019

Tooth defects of EEC and AEC syndrome caused by heterozygous TP63 mutations in three Chinese families and genotype-phenotype correlation analyses of TP63-related disorders.

Mol Genet Genomic Med 2019 06 2;7(6):e704. Epub 2019 May 2.

Department of Prosthodontics, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, China.

Background: Ectrodactyly-Ectodermal dysplasia-Cleft lip/palate (EEC) syndrome and Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome belong to p63 syndromes, a group of rare disorders exhibiting a wide variety of clinical manifestations. TP63 mutations have been reported to be associated with both EEC and AEC.

Methods: Analysis of whole exome sequencing (WES) from patients with EEC or AEC syndrome and Sanger sequencing from family members.

Results: We confirmed that three Chinese pedigrees affected with EEC or AEC harboring a distinct TP63 mutation, and described novel clinical phenotypes of EEC and AEC, including the presence of cubitus valgus deformity and taurodontism, which were discordant to their classical disease features. We also analyzed the genotype-phenotype correlation based on our findings.

Conclusion: We reported that the cubitus valgus deformity in patients with EEC and severe taurodontism in a patient with AEC had not been mentioned previously. Our study expands the phenotypic spectrum of EEC and AEC syndrome.
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http://dx.doi.org/10.1002/mgg3.704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565570PMC
June 2019

One-Step Synthesis of Silica-Coated Carbon Dots with Controllable Solid-State Fluorescence for White Light-Emitting Diodes.

Small 2019 Jun 2;15(24):e1901161. Epub 2019 May 2.

State Key Laboratory of Molecular Engineering of Polymers, Department of Materials Science, Fudan University, Shanghai, 200433, P. R. China.

Carbon dots (CDots)-based solid-state luminescent materials have important applications in light-emitting devices owing to their outstanding optical properties. However, it still remains a challenge to develop multiple-color-emissive solid-state CDots, due to the serious self-quenching of the CDots in the aggregation or solid state. Herein, a one-step synthesis of multiple-color-emissive solid-state silica-coated CDots (silica/CDots) composites by controlling CDots loading fraction and composite morphology to realize the adjustment of emitting color is reported. The emission of resultant silica/CDots composites shifts from blue to orange with the photoluminescence quantum yields of 57.9%, 34.3%, and 32.7% for blue, yellow, and orange emitting, respectively. Furthermore, the yellow emitting silica/CDots composites exhibit an excellent fluorescence thermal stability, and further have been applied to fabricate white-light-emitting devices with a high color rendering index of above 80.
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http://dx.doi.org/10.1002/smll.201901161DOI Listing
June 2019

Newcastle disease virus infection triggers HMGB1 release to promote the inflammatory response.

Virology 2018 12 11;525:19-31. Epub 2018 Sep 11.

Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, PR China. Electronic address:

High mobility group box 1 (HMGB1) is a key member of the "danger associated molecular patterns" (DAMPs) which plays important roles in systemic inflammation and has a pathogenic role in infectious diseases like viral or bacterial infections. Newcastle disease virus (NDV) infection is proved to cause intense inflammatory responses that result in excessive cellular apoptosis and tissue damage, but the function of HMGB1 in NDV-induced cytokine storm has not been elucidated. Here, we report that HMGB1 is a significant inflammation factor in NDV infection. HMGB1 is widely distributed in chicken tissues, and the secretion of it was induced by NDV infection both in DF-1 and A549 cells. Moreover, inhibiting the secretion of HMGB1, NDV replication was not significantly reduced, but it is involved in NDV-induced NF-κB activation and the inflammatory response. Further investigation showed that HMGB1 promotes inflammatory cytokine production through the RAGR, TLR2, and TLR4 receptors. HMGB1-RAGE interaction also takes parts in activation of ERK1/2 and JNK induced by NDV infection. Neutralizing HMGB1 in vivo, chicken viability was increased. Pathological changes and inflammatory cytokines expression were reduced under NDV infection, which further confirmed the pathogenic roles of HMGB1 in inflammatory responses. Thus, our findings show that HMGB1 contributes to the inflammatory cytokine storm induced by NDV infection, which played a critical role in viral pathogenesis.
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http://dx.doi.org/10.1016/j.virol.2018.09.001DOI Listing
December 2018

Facile Synthesis of a Terephthalic Acid-Based Organic Fluorophore with Strong and Color-Tunable Emission in Both Solution and Solid States for LED Applications.

ACS Appl Mater Interfaces 2018 Oct 19;10(39):33390-33398. Epub 2018 Sep 19.

Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Advanced Coatings Research Center of Ministry of Education of China , Fudan University , Shanghai 200433 , China.

Dual-state emission (DSE) fluorophores with strong photoluminescence in both solution and solid states have wide applications in fluorescent probes and photoelectric devices. However, most of the existing DSE fluorophores involve complex synthetic strategies or only one or two emission colors in the solid state, which may hinder their practical applications. Herein, we report a facile and effective strategy to fabricate a kind of novel adjustable DSE fluorophore TPAA-Cu based on the small molecule terephthalic acid (TPA) and ascorbic acid (AA) with CuCl as the catalyst. Not only can the TPAA-Cu solution emit blue, blue-green, and yellow colors depending upon the pH of solution, but also it shows reversible pH-tunable fluorescence colors. More importantly, corresponding TPAA-Cu solid fluorophores with blue, blue-green, and yellow colors can also be obtained with the quantum yields of 16.3, 26.7, and 29.6%, respectively.
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http://dx.doi.org/10.1021/acsami.8b13352DOI Listing
October 2018

Newcastle disease virus induces G/G cell cycle arrest in asynchronously growing cells.

Virology 2018 07 26;520:67-74. Epub 2018 May 26.

Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China. Electronic address:

The cell cycle, as a basic cellular process, is conservatively regulated. Consequently, subversion of the host cell replication cycle is a common strategy employed by many viruses to create a cellular environment favorable for viral replication. Newcastle disease virus (NDV) causes disease in poultry and is also an effective oncolytic agent. However, the effects of NDV infection on cell cycle progression are unknown. In this study, we showed that NDV replication in asynchronized cells resulted in the accumulation of infected cells in the G/G phase of the cell cycle, which benefitted the proliferation of NDV. Examination of various cell cycle-regulatory proteins showed that expression of cyclin D1, was significantly reduced following NDV infection. Importantly, the decreased expression of cyclin D1 was reversed by inhibition of CHOP expression, indicating that induction of the PERK-eIF-2a-ATF4-CHOP signaling pathway was involved in the G/G phase cell cycle arrest observed following NDV infection.
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http://dx.doi.org/10.1016/j.virol.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112094PMC
July 2018

Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I.

Int J Pediatr Otorhinolaryngol 2018 Jan 16;104:200-204. Epub 2017 Nov 16.

Department of Otorhinolaryngology, Hainan General Hospital, Haikou 570311, China. Electronic address:

Objectives: Waardenburg syndrome mutations are most often recurrent or de novo. The rate of familial recurrence is low and families with several affected children are extremely rare. In this study, we aimed to clarify the underlying hereditary cause of Waardenburg syndrome type I in two siblings in a Chinese family, with a mother affected by prelingual mild hearing loss and a father who was negative for clinical symptoms of Waardenburg syndrome and had a normal hearing threshold.

Methods: Complete characteristic features of the family members were recorded and genetic sequencing and parent-child relationship analyses were performed.

Results: The two probands were found to share double mutations in the PAX3/GJB2 genes that caused concurrent hearing loss in Waardenburg syndrome type I. Their mother carried the GJB2 c.109G > A homozygous mutation; however, neither the novel PAX3 c.592delG mutation, nor the Waardenburg syndrome phenotype, was observed in either parent.

Conclusion: These previously unreported digenic mutations in PAX3/GJB2 resulted in deafness associated with Waardenburg syndrome type I in this family. To our knowledge, this is the first report describing germinal mosaicism in Waardenburg syndrome. This concept is important because it complicates genetic counseling of this family regarding the risk of recurrence of the mutations in subsequent pregnancies.
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http://dx.doi.org/10.1016/j.ijporl.2017.11.011DOI Listing
January 2018

Multistimulative Nanogels with Enhanced Thermosensitivity for Intracellular Therapeutic Delivery.

ACS Appl Mater Interfaces 2017 Nov 3;9(45):39143-39151. Epub 2017 Nov 3.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University , Wuhan 430062, People's Republic of China.

The flexibility and hydrophilicity of nanogels suggest their potential for the creation of nanocarriers with good colloidal stability and stimulative ability. In the present study, biocompatible AGP and AGPA nanogels with triple-stimulative properties (thermosensitivity, pH sensitivity, and redox sensitivity) were prepared by incorporating poly(N-isopropylacrylamide) (PNIPAM) or poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) into alginate (AG) emulsion nanodrops, followed by fixation with a disulfide-containing molecule (cystamine dihydrochloride (Cys)). Compared to AG/PNIPAM(AGP) nanogels, AG/P(NIPAM-AA) (AGPA) nanogels exhibited more sensitive volumetric expansion by switching the temperature from 40 to 25 °C under physiological medium. This expansion occurs because P(NIPAM-AA) with -COOH groups can be fixed inside the nanogels via chemical bonding with Cys, whereas PNIPAM was encapsulated in the nanogels through simple physical interactions with the AG matrix. AGPA nanogels carrying an anticancer drug tend to easily enter cells upon heating, thereby exerting toxicity through a cold shock and reverse thermally induced release of an anticancer drug. Upon internalization inside cells, the nanogels use the reducible and acidic intracellular environments to effectively release the drug to the nucleus to impart anticancer activity. These results demonstrate that multifunctional nanogels may be used as a general platform for therapeutic delivery.
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http://dx.doi.org/10.1021/acsami.7b08209DOI Listing
November 2017

Phylogenetic, antigenic and biological characterization of pigeon paramyxovirus type 1 circulating in China.

Virol J 2017 09 29;14(1):186. Epub 2017 Sep 29.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, People's Republic of China.

Background: For many years, ND has been one of the most important infectious pigeon diseases in China. In recent years, a high mortality has been observed in ND-infected pigeons in China. Mortality is from 40% to 80% or 100% in some cases.

Methods: The full-length genomes of four pigeon paramyxovirus type 1 (PPMV-1) strains, which were isolated from infected pigeons in China in 2012 and 2013, were sequenced and analyzed to determine the phylogenetic characteristics of PPMV-1 circulating in pigeons of China in recent years. Furthermore, cross hemagglutination inhibition and cross virus neutralization assays, as well as animal experiments were conducted to determine the antigenicity and pathogenicity of those viruses. Proteolytic cleavage sites (residues 112-117) of the F proteins were identified as the typical virulence motif, RRQKR↓F for all four PPMV-1 strains investigated.

Results: Phylogenetic analysis based on sequences of complete genomes and F gene revealed that the four PPMV-1 isolates and most of recent isolates in China were highly homologous to European isolates from 1998 to 2011. All those isolates were clustered in one clade of genotype VI NDV, termed as subgroup 4bii f. The R value was calculated based on cross hemagglutination inhibition and cross virus neutralization results, and confirmed antigenic difference of the PPMV-1 strains isolated in 2013 from the LaSota vaccine strain. Several mutations were identified in the surface glycoproteins F and HN, which probably gave rise to those antigenic differences.

Conclusion: Our result suggested that the PPMV-1 strain prevailing in China in the last decade diverged from a common ancestor and was presumably transmitted from Europe. PPMV-1 isolates displayed obvious antigenic differences from vaccine strain LaSota. Even though PPMV-1 did not cause high mortality in experimental pigeons, the infected pigeons were exhibiting viral shedding for 3 weeks after infection, suggesting PPMV-1 is a potential threat to NDV control worldwide.
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http://dx.doi.org/10.1186/s12985-017-0857-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622419PMC
September 2017

Study on β-cyclodextrin-complexed nanogels with improved thermal response for anticancer drug delivery.

Mater Sci Eng C Mater Biol Appl 2017 Sep 19;78:773-779. Epub 2017 Apr 19.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, People's Republic of China. Electronic address:

For achievement of controllability in drug delivery, development of nanocarriers with thermal response is one of the most investigated stimulative strategies for oncological treatment. How to improve the thermosensitivity of the nanocarriers is an important factor for their successful drug delivery applications. In this study, a kind of complexed nanogels (PNACD) was developed by incorporating β-cyclodextrin (β-CD) into the nanogels of copolymers of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) during their polymerization via in situ crosslinking of N,N'-methylenebisacrylamide (MBA) as a crosslinker. The complexed PNACD nanogels displayed a significantly enhanced thermosensitivity near body temperature compared to the β-CD-free nanogels (PNA), which is probably associated with the rapid volumetric transformation during heating/cooling process due to the formation of complexed (decomplexed) structure between β-CD and PNIPAM element. The PNACD nanogels can be used for loading of an anticancer drug (doxorubicin, DOX) with an encapsulation efficiency of 54±5%. The DOX-loaded nanogels displayed pH-/thermo-dual responsivenesses in drug release, which can be effectively internalized into KB cells (a human epithelial carcinoma cell line) to exert good anticancer bioactivity. This approach may enlighten design of novel nanocarriers for delivery of drugs beyond anticancer chemotherapeutic reagents.
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http://dx.doi.org/10.1016/j.msec.2017.04.096DOI Listing
September 2017

Specific Monoclonal Antibodies Recognizing the Endogenous Chicken High Mobility Group Box 1 Protein.

Monoclon Antib Immunodiagn Immunother 2017 Aug 1;36(4):163-168. Epub 2017 Jun 1.

Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute , Chinese Academy of Agricultural Science, Shanghai, People's Republic of China .

High mobility group box 1 (HMGB1) is a key member of the "danger associated molecular patterns" (DAMPs), which can localize in various compartments of the cell, and plays important roles in systemic inflammation. In the present study, monoclonal antibodies (MAbs) specifically against chicken HMGB1 were generated. The open reading frame of chicken HMGB1 was amplified by RT-PCR and cloned into the prokaryotic expression vector pET-28a to construct a recombinant plasmid pET-chHMGB1. The recombinant chicken HMGB1 protein was expressed in Escherichia coli Rosetta under IPTG induction and then purified by Ni-NTA Purification System. BALB/c mice were immunized with the purified recombinant HMGB1 protein, and three strains of hybridoma cells named 1F10, 8C11, and 4D8 secreting MAbs of chicken HMGB1 were obtained by hybridoma technique. Western blot and indirect immunofluorescence assays showed that the endogenous HMGB1 in various cell lines and glycosylated HMGB1 could both be specifically recognized by the prepared MAbs. This work indicated that the MAbs against chicken HMGB1 would be a valuable tool for further studies of HMGB1-mediated signaling in virus-infected cells and investigates the role of HMGB1 in avian virus pathogenesis.
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http://dx.doi.org/10.1089/mab.2017.0010DOI Listing
August 2017

Stimulative nanogels with enhanced thermosensitivity for therapeutic delivery via β-cyclodextrin-induced formation of inclusion complexes.

Carbohydr Polym 2017 Jun 1;166:219-227. Epub 2017 Mar 1.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China. Electronic address:

To explore the potential biomedical application of thermoresponsive nanosystems, it is important to enhance their thermosensitivity to improve the controllability in delivery of therapeutic agents. The present work develops multifunctional nanogels with enhanced thermosensitivity through copolymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of β-cyclodextrin (β-CD), using N,N'-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker. The resulting nanogels display significantly improved sensitivity in deswelling (swelling) behavior upon temperature increase (decrease) around body temperature. The nanogels can effectively encapsulate doxorubicin (DOX), which can be released in an accelerated way under microenvironments that mimic intracellular reductive conditions and acidic tumor tissues. Release can also be remotely manipulated by increasing temperature. In vitro study indicates that the nanogels are quickly taken up by KB cells (a human epithelial carcinoma cell line), exerting improved anticancer cytotoxicity, showing their potential for delivery of therapeutic agents beyond anticancer drugs.
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http://dx.doi.org/10.1016/j.carbpol.2017.02.107DOI Listing
June 2017

Newcastle disease virus induces stable formation of stress granules to facilitate viral replication through manipulating host protein translation.

FASEB J 2017 04 23;31(4):1337-1353. Epub 2016 Dec 23.

Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, China;

Mammalian cells respond to various environmental stressors to form stress granules (SGs) by arresting cytoplasmic mRNA, protein translation element, and RNA binding proteins. Virus-induced SGs function in different ways, depending on the species of virus; however, the mechanism of SG regulation of virus replication is not well understood. In this study, Newcastle disease virus (NDV) triggered stable formation of SGs on HeLa cells through activating the protein kinase R (PKR)/eIF2α pathway. NDV-induced SGs contained classic SG markers T-cell internal antigen (TIA)-1, Ras GTPase-activating protein-binding protein (G3BP)-1, eukaryotic initiation factors, and small ribosomal subunit, which could be disassembled in the presence of cycloheximide. Treatment with nocodazole, a microtubule disruption drug, led to the formation of relatively small and circular granules, indicating that NDV infection induces canonical SGs. Furthermore, the role of SGs on NDV replication was investigated by knockdown of TIA-1 and TIA-1-related (TIAR) protein, the 2 critical components involved in SG formation from the HeLa cells, followed by NDV infection. Results showed that depletion of TIA-1 or TIAR inhibited viral protein synthesis, reduced extracellular virus yields, but increased global protein translation. FISH revealed that NDV-induced SGs contained predominantly cellular mRNA rather than viral mRNA. Deletion of TIA-1 or TIAR reduced NP mRNA levels in polysomes. These results demonstrate that NDV triggers stable formation of SGs, which benefit viral protein translation and virus replication by arresting cellular mRNA.-Sun, Y., Dong, L., Yu, S., Wang, X., Zheng, H., Zhang, P., Meng, C., Zhan, Y., Tan, L., Song, C., Qiu, X., Wang, G., Liao, Y., Ding, C. Newcastle disease virus induces stable formation of stress granules to facilitate viral replication through manipulating host protein translation.
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http://dx.doi.org/10.1096/fj.201600980RDOI Listing
April 2017

Newcastle disease virus employs macropinocytosis and Rab5a-dependent intracellular trafficking to infect DF-1 cells.

Oncotarget 2016 Dec;7(52):86117-86133

Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, P.R. China.

Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed. NDV entry into cells triggers Rac1-Pak1 signaling and elicits actin rearrangement and plasma membrane ruffling. Moreover, NDV internalization within macropinosomes and trafficking involve Rab5a-positive vesicles. This is the first report demonstrating that NDV utilizes clathrin-mediated endocytosis and macropinocytosis as alternative endocytic pathways to enter cells. These findings shed new light on the molecular mechanisms underlying NDV entry into cells, and provide potential targets for NDV-mediated therapy in cancer.
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http://dx.doi.org/10.18632/oncotarget.13345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349901PMC
December 2016

Infectious bronchitis virus poly-epitope-based vaccine protects chickens from acute infection.

Vaccine 2016 10 21;34(44):5209-5216. Epub 2016 Sep 21.

Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China. Electronic address:

Infectious bronchitis virus (IBV) causes major losses in the poultry industry. The safe and effective vaccine to control IBV spread is imperative. In the present study, we developed IBV S1 glycoprotein poly-epitope-based DNA vaccine pV-S1B+S1T consisting of SH1208 and Holte strain BF2-restricted T cell epitopes and Australian T strain dominant B cell neutralization epitopes. Specific pathogen-free chickens were vaccinated with pV-S1B+S1T and control plasmids twice to elicit strong humoral and cellular immune response, as indicated by viral neutralization titers and results of CD8 T cell proliferation assays. A lethal dose of IBV SH1208 strain used for protection and challenge experiments at two weeks post-booster immunization following challenge protection and virus shedding reverse transcription quantitative PCR assay, indicated that pV-S1B+S1T protected against IBV and significantly reduced viral excretion. These results demonstrated that the IBV poly-epitope-based vaccine effectively prevents infection and represents a potential IBV vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2016.09.022DOI Listing
October 2016

Infectious bronchitis virus poly-epitope-based vaccine protects chickens from acute infection.

Vaccine 2016 10 21;34(44):5209-5216. Epub 2016 Sep 21.

Department of Avian Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China. Electronic address:

Infectious bronchitis virus (IBV) causes major losses in the poultry industry. The safe and effective vaccine to control IBV spread is imperative. In the present study, we developed IBV S1 glycoprotein poly-epitope-based DNA vaccine pV-S1B+S1T consisting of SH1208 and Holte strain BF2-restricted T cell epitopes and Australian T strain dominant B cell neutralization epitopes. Specific pathogen-free chickens were vaccinated with pV-S1B+S1T and control plasmids twice to elicit strong humoral and cellular immune response, as indicated by viral neutralization titers and results of CD8 T cell proliferation assays. A lethal dose of IBV SH1208 strain used for protection and challenge experiments at two weeks post-booster immunization following challenge protection and virus shedding reverse transcription quantitative PCR assay, indicated that pV-S1B+S1T protected against IBV and significantly reduced viral excretion. These results demonstrated that the IBV poly-epitope-based vaccine effectively prevents infection and represents a potential IBV vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2016.09.022DOI Listing
October 2016

Interferon regulatory factor 3 is a key regulation factor for inducing the expression of SAMHD1 in antiviral innate immunity.

Sci Rep 2016 07 14;6:29665. Epub 2016 Jul 14.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.

SAMHD1 is a type I interferon (IFN) inducible host innate immunity restriction factor that inhibits an early step of the viral life cycle. The underlying mechanisms of SAMHD1 transcriptional regulation remains elusive. Here, we report that inducing SAMHD1 upregulation is part of an early intrinsic immune response via TLR3 and RIG-I/MDA5 agonists that ultimately induce the nuclear translocation of the interferon regulation factor 3 (IRF3) protein. Further studies show that IRF3 plays a major role in upregulating endogenous SAMHD1 expression in a mechanism that is independent of the classical IFN-induced JAK-STAT pathway. Both overexpression and activation of IRF3 enhanced the SAMHD1 promoter luciferase activity, and activated IRF3 was necessary for upregulating SAMHD1 expression in a type I IFN cascade. We also show that the SAMHD1 promoter is a direct target of IRF3 and an IRF3 binding site is sufficient to render this promoter responsive to stimulation. Collectively, these findings indicate that upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3 and we suggest that type I IFN induction and induced SAMHD1 expression are coordinated.
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http://dx.doi.org/10.1038/srep29665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944147PMC
July 2016

The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis.

Arch Virol 2016 Sep 29;161(9):2491-501. Epub 2016 Jun 29.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Newcastle disease (ND) is a contagious disease that affects most species of birds. Its causative pathogen, Newcastle disease virus (NDV), also exhibits considerable oncolytic activity against mammalian cancers. A better understanding of the pathogenesis of NDV will help us design efficient vaccines and novel anticancer strategies. GW3965, a widely used synthetic ligand of liver X receptor (LXR), induces the expression of LXRs and its downstream genes, including ATP-binding cassette transporter A1 (ABCA1). ABCA1 regulates cellular cholesterol homeostasis. Here, we found that GW3965 inhibited NDV infection in DF-1 cells. It also inhibited NF-κB activation and reduced the upregulation of proinflammatory cytokines induced by the infection. Further studies showed that GW3965 exerted its inhibitory effects on virus entry and replication. NDV infection increased the mRNA levels of several lipogenic genes but decreased the ABCA1 mRNA level. Overexpression of ABCA1 inhibited NDV infection and reduced the cholesterol content in DF-1 cells, but when the cholesterol was replenished, NDV infection was restored. GW3965 treatment prevented cholesterol accumulation in the perinuclear area of the infected cells. In summary, our studies suggest that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis.
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http://dx.doi.org/10.1007/s00705-016-2950-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087268PMC
September 2016

Newcastle disease virus infection induces activation of the NLRP3 inflammasome.

Virology 2016 09 3;496:90-96. Epub 2016 Jun 3.

Shanghai Veterinary Research Institute, CAAS, Shanghai 200241, China. Electronic address:

Inflammatory responses are important aspects of the innate immune system during virus infection. We found that Newcastle disease virus can induce inflammasome activation in the human macrophage-like cell line THP-1. Viral replication was required for inflammasome activation, and small hairpin RNA knockdown experiments indicated that IL-1β secretion was mediated by the NLRP3 inflammasome. We also verified the results in LPS-primed bone marrow-derived macrophages (BMDMs) from NLRP3-deficient and wild type mice. NDV is considered to be a promising oncolytic virus. Stimulating the immune system has been proposed as a key mechanism of oncolytic specificity, and the inflammasome appears to be an important mechanism by which NDV is controlled. Knockdown of inflammasome components or chemical inhibition of caspase-1 activity shows that cell survival was augmented and benefited NDV replication. This study shows that NLRP3 inflammasome activation is an innate cellular response to NDV infection and offers insights into the oncolytic specificity of NDV.
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http://dx.doi.org/10.1016/j.virol.2016.05.023DOI Listing
September 2016

Identification and functional analysis of phosphorylation in Newcastle disease virus phosphoprotein.

Arch Virol 2016 Aug 9;161(8):2103-16. Epub 2016 May 9.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, People's Republic of China.

Newcastle disease virus (NDV) encodes a highly phosphorylated P protein; however, the phosphorylation sites have not been identified, and the relationship between phosphorylation and protein function is still unclear. In this study, we bioinformatically predicted 26 amino acid residues in the P protein as potential phosphorylation sites. Furthermore, we treated infected cells with kinase inhibitors to investigate NDV propagation and found that protein kinase C (PKC) is involved in the NDV life cycle and that PKC-activated phosphorylation functions in NDV replication. Using an NDV minigenome assay, we found that expression of a reporter protein decreased when the minigenome system contained P mutants lacking T44, S48, T271, S373 and especially T111. The phosphorylation status of S48, T111, S125 and T271 was determined by Phos-tag SDS-PAGE analysis. Coimmunoprecipitation assays showed that the binding activity of NP and the P-T111A mutant was stronger than that of NP and the wild-type P, suggesting that P-T111 is involved in NP-P interaction. This study sheds light on the mechanism by which P protein phosphorylation affects NDV replication and transcription.
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http://dx.doi.org/10.1007/s00705-016-2884-xDOI Listing
August 2016

Newcastle Disease Virus V Protein Targets Phosphorylated STAT1 to Block IFN-I Signaling.

PLoS One 2016 9;11(2):e0148560. Epub 2016 Feb 9.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Minhang, Shanghai, China.

Newcastle disease virus (NDV) V protein is considered as an effector for IFN antagonism, however, the mechanism remains unknown. In this study, the expression of STAT1 and phospho-STAT1 in cells infected with NDV or transfected with V protein-expressing plasmids were analyzed. Our results showed that NDV V protein targets phospho-STAT1 reduction in the cells depends on the stimulation of IFN-α. In addition, a V-deficient genotype VII recombinant NDV strain rZJ1-VS was constructed using reverse genetic technique to confirm the results. The rZJ1-VS lost the ability to reduce phospho-STAT1 and induced higher expression of IFN-responsive genes in infected cells. Furthermore, treatment with an ubiquitin E1 inhibitor PYR-41 demonstrated that phospho-STAT1 reduction was caused by degradation, but not de-phosphorylation. We conclude that NDV V protein targets phospho-STAT1 degradation to block IFN-α signaling, which adds novel knowledge to the strategies used by paramyxoviruses to evade IFN.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148560PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747598PMC
July 2016