Suzhou Institute of Systems Medicine

Suzhou, China

Suzhou Institute of Systems Medicine

Suzhou, China
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Wang L.,Peking Union Medical College | Wang L.,Suzhou Institute of Systems Medicine | Wang L.,University of California at Los Angeles | Liu S.-Y.,University of California at Los Angeles | And 29 more authors.
Cell Host and Microbe | Year: 2017

New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones. © 2017 Elsevier Inc.


Zou Y.,Hunan University | Wu Z.,Hunan University | Deng L.,Peking Union Medical College | Deng L.,Suzhou Institute of Systems Medicine | And 7 more authors.
Bioinformatics | Year: 2017

Motivation: Previously, we developed a computational model to identify genomic co-occurrence networks that was applied to capture the coevolution patterns within genomes of influenza viruses. To facilitate easy public use of this model, an R package'cooccurNet' is presented here. Results:'cooccurNet' includes functionalities of construction and analysis of residues (e.g. nucleotides, amino acids and SNPs) co-occurrence network. In addition, a new method for measuring residues coevolution, defined as residue co-occurrence score (RCOS), is proposed and implemented in'cooccurNet' based on the co-occurrence network. Availability and Implementation:'cooccurNet' is publicly available on CRAN repositories under the GPL-3 Open Source License (http://cran.r-project.org/package=cooccurNet) © The Author 2017. Published by Oxford University Press. All rights reserved.


Wang Z.,Sun Yat Sen University | Ji J.,Sun Yat Sen University | Peng D.,Sun Yat Sen University | Ma F.,Peking Union Medical College | And 8 more authors.
Journal of Immunology | Year: 2016

Induction of type I IFN (IFN-I) is essential for host antiviral immune responses. However, IFN-I also plays divergent roles in antibacterial immunity, persistent viral infections, autoimmune diseases and tumorigenesis. IFN regulatory factor 3 (IRF3) is the master transcription factor that controls IFN-I production via phosphorylation-dependent dimerization in most cell types in response to viral infections and various innate stimuli by pathogen-associated molecular patterns (PAMPs). To monitor the dynamic process of IRF3 activation, we developed a novel IRF3 dimerization reporter based on bimolecular luminescence complementation (BiLC) techniques, termed the IRF3-BiLC reporter. Robust induction of luciferase activity of the IRF3-BiLC reporter was observed upon viral infection and PAMP stimulation with a broad dynamic range. Knockout of TANK-binding kinase 1, the critical upstream kinase of IRF3, as well as the mutation of serine 386, the essential phosphorylation site of IRF3, completely abolished the luciferase activity of IRF3-BiLC reporter, confirming the authenticity of IRF3 activation. Taken together, these results demonstrated that the IRF3-BiLC reporter is a highly specific, reliable, and sensitive system to measure IRF3 activity. Using this reporter system, we further observed that the temporal pattern and magnitude of IRF3 activation induced by various PAMPs are highly complex with distinct cell type-specific characteristics, and IRF3 dimerization is a direct regulatory node for IFN-α/β receptor-mediated feedforward regulation and crosstalk with other pathways. Therefore, the IRF3-BiLC reporter has multiple potential applications, including mechanistic studies as well as the identification of novel compounds that can modulate IRF3 activation. Copyright © 2016 by The American Association of Immunologists, Inc.


Di P.,Sun Yat Sen University | Zining W.,Sun Yat Sen University | Anfei H.,Peking Union Medical College | Anfei H.,Suzhou Institute of Systems Medicine | And 3 more authors.
Journal of Immunology | Year: 2017

The F-box proteins were originally identified as the key component of SKP1-Cullin1-F-box E3 ligase complexes that control the stability of their specific downstreamsubstrates essential for cell growth and survival. However, the involvement of these proteins in type I IFN (IFN-I) signaling during innate immunity has not been investigated. In this study we report that the F-box protein FBXO17 negatively regulates IFN-I signaling triggered by double-strand DNA, RNA, or viral infection. We found that FBXO17 specifically interacts with IFN regulatory factor 3 (IRF3) and decreases its dimerization and nuclear translocation. The decrease of IRF3 dimerization and nuclear translocation is due to the recruitment of protein phosphatase 2 (PP2A) mediated by FBXO17, resulting in IRF3 dephosphorylation. Interestingly, PP2A recruitment does not require the F-box domain but instead the F-box associated region of the protein; thus, the recruitment is independent of the canonical function of the SKP1-Cullin1-F-box family of E3 ligase. Together, our studies identify a previously unreported role of FBXO17 in regulating IFN-I signaling and further demonstrate a novel mechanism for IRF3 deactivation by F-box protein-mediated recruitment of PP2A. Copyright © 2017 by The American Association of Immunologists, Inc.


PubMed | CAS Institute of Biophysics, University of Science and Technology of China, Suzhou Institute of Systems Medicine, China Institute of Metrology and 3 more.
Type: Journal Article | Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2016

The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair (MMR) function on the tumorigenesis of colorectal cancer.The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 (hRad9) gene in these samples were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. The plasmid of pFLAG-hRad9 (L101M) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9-deleted mouse cells (mRad9(-/-) cells). The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function.Mutation from Leu to Met at the residue 101 (L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9(-/-)+ L101M cells (mRad9-deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.05.6)%, which was significantly lower than that in the mRad9(-/-)+ hRad9 cells [mRad9-deleted mouse cells with ectopic expression of hRad9 gene, (48.07.5)%, P<0.05]. After N-nitroso-N-methylurea (MNU) treatment, the survival rate of mRad9(-/-)+ L101M cells was (33.75.9)%, which was significantly higher than that in the mRad9(-/-)+ hRad9 cells [(21.34.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post-translational modification in mRad9(-/-) cells also led to a reduced MMR activity.Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.


Liu W.,Shanghai JiaoTong University | Liu W.,Suzhou Institute of Systems Medicine | Wu A.,Suzhou Institute of Systems Medicine | Wu A.,Chinese Institute of Basic Medical Sciences
Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 | Year: 2015

Recent advances in proteomic technologies have enabled high-throughput binary data on protein-protein interactions of E. coli to be released into public domain, and many protein complexes have been identified by experimental methods. Although it has a long study history, a large-scale analysis of protein complex in binary PPI network of E. coli is still absent. We used a novel link clustering algorithm named ELPA to infer protein complexes and functional modules in E. coli PPI network. By mapping our results to 276 gold standard protein complexes and protein function annotations offered by EcoCyc, we found that 80.2% of predicted modules mapping well with one or more complexes, while 92.8% of predicted modules tally well with certain GO terms. Furthermore, we compare our results with MCL algorithm, and evaluated our results with several accuracy measures and biological relevance, the result shows that ELPA achieved an average 18.3% improvement over MCL based on the accuracy measures, which means our method will contributes to uncover the complexes of Ecoli. © 2015 IEEE.


Wang L.,Peking Union Medical College | Wang L.,Suzhou Institute of Systems Medicine | Valderramos S.,University of California at Los Angeles | Wu A.,Peking Union Medical College | And 12 more authors.
Cell Host and Microbe | Year: 2016

Initially isolated in 1947, Zika virus (ZIKV) has recently emerged as a significant public health concern. Sequence analysis of all 41 known ZIKV RNA open reading frames to date indicates that ZIKV has undergone significant changes in both protein and nucleotide sequences during the past half century. Initially isolated in 1947, Zika virus (ZIKV) has recently emerged as a significant public health concern. Sequence analysis of all 41 known ZIKV RNA open reading frames to date indicates that ZIKV has undergone significant changes in both protein and nucleotide sequences during the past half century. © 2016 Elsevier Inc.


Peng Y.,Hunan University | Yang L.,Chinese National Institute for Viral Disease Control and Prevention | Li H.,Hunan University | Zou Y.,Hunan University | And 10 more authors.
Bioinformatics | Year: 2016

Motivation: Timely surveillance of the antigenic dynamics of the influenza virus is critical for accurate selection of vaccine strains, which is important for effective prevention of viral spread and infection. Results: Here, we provide a computational platform, called PREDAC-H3, for antigenic surveillance of human influenza A(H3N2) virus based on the sequence of surface protein hemagglutinin (HA). PREDAC-H3 not only determines the antigenic variants and antigenic cluster (grouped for similar antigenicity) to which the virus belongs, based on HA sequences, but also allows visualization of the spatial distribution and temporal dynamics of antigenic clusters of viruses isolated from around the world, thus assisting in antigenic surveillance of human influenza A(H3N2) virus. © 2016 The Author 2016. Published by Oxford University Press. All rights reserved.


Peng Y.,Hunan University | Wang D.,Chinese National Institute for Viral Disease Control and Prevention | Shu Y.,Chinese National Institute for Viral Disease Control and Prevention | Jiang T.,Peking Union Medical College | Jiang T.,Suzhou Institute of Systems Medicine
Virologica Sinica | Year: 2016

[Figure not available: see fulltext.] © 2016 Wuhan Institute of Virology, CAS and Springer Science+Business Media Singapore


Ci X.,Jilin University | Lv H.,Jilin University | Wang L.,Jilin University | Wang X.,Jilin University | And 9 more authors.
Chemico-Biological Interactions | Year: 2015

Abstract Farrerol, (S)-2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-dimethyl-4-benzopyrone, isolated from rhododendron, has been shown to have antioxidative potential, but the molecular mechanism underlying this activity remains unclear. The inducible expression of heme oxygenase-1 (HO-1), a potent antioxidative and cytoprotective enzyme, is known to play an important role in cytoprotection in a variety of pathological models. In this study, we evaluated the antioxidative potential of farrerol against oxidative damage and investigated its antioxidative mechanism in RAW 264.7 cells. The molecular mechanism underlying the cytoprotective function of farrerol was determined by analyzing intracellular signaling pathways, transcriptional activation and the inhibitory effect of HO-1 on ROS production. Farrerol induced antioxidant enzymes mRNA expression, HO-1 protein expression and nuclear translocation of NF-E2-related factor 2 in RAW 264.7 macrophage cells. Farrerol down-regulated the expression of the Keap1 protein and the thiol reducing agents attenuated farrerol-induced HO-1 expression. Further investigation utilizing Western blotting and specific inhibitors of Akt, p38, JNK and ERK demonstrated that Akt, p38, and ERK axis of signaling pathway mediates HO-1 expression. Moreover, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was ameliorated by farrerol treatment in a dose-dependent manner, which was abolished by Akt, p38, ERK and HO-1 inhibitors (Snpp). It is hence likely that farrerol inactivated KEAP-1 or activated the Akt, p38 and ERK to facilitate the release of Nrf2 from Keap1 and subsequent reduced the intracellular production of reactive oxygen species via the induction of HO-1 expression. These results support the central role of HO-1 in the cytoprotective effect of farrerol. © 2015 Elsevier Ireland Ltd.

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