12 results on '"Fengwen Xu"'
Search Results
2. Chemokine (C-X-C Motif) Ligand 4 Is a Restrictor of Respiratory Syncytial Virus Infection and an Indicator of Clinical Severity
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Jian Rao, Zhengde Xie, Junlin Zhu, Fei Guo, Han Zibo, Xiaobo Lei, Zhendong Zhao, Fengwen Xu, Baoping Xu, Yingying Wang, Bin Yang, Suyun Qian, Conghui Wang, Lili Ren, and Jianwei Wang
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Male ,Pulmonary and Respiratory Medicine ,Chemokine ,viruses ,Respiratory Syncytial Virus Infections ,Ligands ,Critical Care and Intensive Care Medicine ,Antiviral Agents ,Severity of Illness Index ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Humans ,Medicine ,Clinical severity ,030212 general & internal medicine ,Respiratory system ,biology ,business.industry ,Infant, Newborn ,Editorials ,Infant ,Treatment options ,Virology ,030228 respiratory system ,Child, Preschool ,Respiratory Syncytial Virus, Human ,DNA, Viral ,biology.protein ,Female ,business ,Chemokines, CXC ,Biomarkers ,Restriction factor - Abstract
Rationale: Respiratory syncytial virus (RSV) is the leading cause of childhood respiratory infections worldwide; however, no vaccine is available, and treatment options are limited. Identification ...
- Published
- 2020
3. Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid
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Jianwei Wang, Quanjie Li, Yu Huang, Shan Mei, Fei Guo, Xiaoxiao Zhao, Liang Wei, Di Zhang, Chao Wu, Xiaoman Liu, Chen Liang, Hong Sun, Siqi Hu, Fengwen Xu, Shan Cen, Zhangling Fan, and Fei Zhao
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Myxovirus Resistance Proteins ,0301 basic medicine ,Proline ,Active Transport, Cell Nucleus ,HIV Infections ,GTPase ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,Capsid ,medicine ,Humans ,Protein oligomerization ,Nuclear export signal ,Molecular Biology ,Dynamin ,Cell Nucleus ,Nuclear Export Signals ,Mutation ,030102 biochemistry & molecular biology ,Chemistry ,Molecular Bases of Disease ,Cell Biology ,3. Good health ,Cell biology ,HEK293 Cells ,030104 developmental biology ,Cytoplasm ,HIV-1 ,Protein Multimerization ,Nuclear localization sequence ,HeLa Cells ,Protein Binding - Abstract
Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505-527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515-519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.
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- 2020
4. Human MxB Inhibits the Replication of Hepatitis C Virus
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Cheng-Feng Qin, Dongrong Yi, Jing An, Leiliang Zhang, Fengwen Xu, Yongxin Zhang, Jinming Zhou, Zhenlong Liu, Fei Guo, Kavita Raniga, Shan Cen, Xiaoyu Li, Ni An, Chen Liang, Jing Wang, Quanjie Li, and Rui Zhou
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Myxovirus Resistance Proteins ,viruses ,Hepatitis C virus ,Immunology ,Cypa ,Hepacivirus ,Viral Nonstructural Proteins ,Biology ,Dengue virus ,Endoplasmic Reticulum ,Virus Replication ,medicine.disease_cause ,Microbiology ,Virus ,Cell Line ,03 medical and health sciences ,Flaviviridae ,Interferon ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,NS5A ,Vero Cells ,030304 developmental biology ,0303 health sciences ,030306 microbiology ,biology.organism_classification ,Virus-Cell Interactions ,3. Good health ,HEK293 Cells ,Viral replication ,Gene Knockdown Techniques ,Insect Science ,Cyclosporine ,Interferons ,Cyclophilin A ,Protein Binding ,medicine.drug - Abstract
Type I interferon (IFN) inhibits viruses by inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses, including HIV-1 and herpesviruses, but its antiviral coverage remains to be explored further. Here we show that MxB interferes with RNA replication of hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with the HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication. Interestingly, we found that MxB significantly inhibits two additional CypA-dependent viruses of the Flaviviridae family, namely, Japanese encephalitis virus and dengue virus, suggesting a potential link between virus dependence on CypA and virus susceptibility to MxB inhibition. Collectively, these data have identified MxB as a key factor behind IFN-mediated suppression of HCV infection, and they suggest that other CypA-dependent viruses may also be subjected to MxB restriction. IMPORTANCE Viruses of the Flaviviridae family cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of the Flaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics.
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- 2019
5. MOV10 sequesters the RNP of influenza A virus in the cytoplasm and is antagonized by viral NS1 protein
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Shan Cen, Jianwei Wang, Zichen Xiong, Di Zhang, Hong Sun, Siqi Hu, Xiaoman Liu, Shan Mei, Chen Liang, Jian Li, Fei Guo, Fengwen Xu, Fei Zhao, Xiaoxiao Zhao, and Lijuan Yin
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Cytoplasm ,viruses ,Hepatitis C virus ,Biology ,Viral Nonstructural Proteins ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,P-bodies ,Influenza A virus ,medicine ,Humans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Host (biology) ,030302 biochemistry & molecular biology ,Cell Biology ,biology.organism_classification ,Virology ,Nucleoprotein ,HEK293 Cells ,Ribonucleoproteins ,Vesicular stomatitis virus ,A549 Cells ,Proteolysis ,Intracisternal A-Particle ,Lysosomes ,RNA Helicases - Abstract
MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses, including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, but also restricts the activity of retroelements long interspersed nucleotide element-1, Alu, SVA and intracisternal A particles. Here, we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein (NP), sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. The antiviral activity of MOV10 depends on the integrity of P-bodies. We also found that the antiviral activity of MOV10 is partially countered by viral NS1 protein that interferes with the interaction of MOV10 with viral NP and causes MOV10 degradation through the lysosomal pathway. Moreover, NS1-defective influenza A virus is more susceptible to MOV10 restriction. Our data not only expand the antiviral spectrum of MOV10 but also reveal the NS1 protein as the first viral antagonist of MOV10.
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- 2018
6. The Interferon-Inducible MxB Protein Inhibits HIV-1 Infection
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Shilei Ding, Chen Liang, Fengwen Xu, Shan Cen, Qinghua Pan, Fei Guo, Zhenlong Liu, Jin Qian, and Jinming Zhou
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Peptidylprolyl isomerase ,0303 health sciences ,Cancer Research ,biology ,030302 biochemistry & molecular biology ,Mutant ,RNA ,Cypa ,biology.organism_classification ,Microbiology ,Virology ,Virus ,3. Good health ,03 medical and health sciences ,Cyclophilin A ,Capsid ,Interferon ,Immunology and Microbiology(all) ,medicine ,Parasitology ,Molecular Biology ,030304 developmental biology ,medicine.drug - Abstract
SummaryThe interferon-inducible myxovirus resistance (Mx) proteins play important roles in combating a wide range of virus infections. MxA inhibits many RNA and DNA viruses, whereas the antiviral activity of MxB is less well established. We find that human MxB inhibits HIV-1 infection by reducing the level of integrated viral DNA. Passaging HIV-1 through MxB-expressing cells allowed the evolution of a mutant virus that escapes MxB restriction. HIV-1 escapes MxB restriction by mutating the alanine residue at position 88 in the viral capsid protein (CA), with a consequent loss of CA interaction with the host peptidylprolyl isomerase cyclophilin A (CypA), suggesting a role for CypA in MxB restriction. Consistent with this, MxB associates with CypA, and shRNA-mediated CypA depletion or cyclosporine A treatment resulted in the loss of MxB inhibition of HIV-1. Taken together, we conclude that human MxB protein inhibits HIV-1 DNA integration by a CypA-dependent mechanism.
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- 2013
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7. BST-2 restricts IAV release and is countered by the viral M2 protein
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Jian Li, Chen Liang, Fengwen Xu, Xiaoman Liu, Siqi Hu, Shan Cen, Fei Guo, Shan Mei, Ailing Li, Lijuan Yin, and Hong Sun
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0301 basic medicine ,Proteasome Endopeptidase Complex ,viruses ,Hemagglutinin (influenza) ,Neuraminidase ,Hemagglutinin Glycoproteins, Influenza Virus ,Biology ,medicine.disease_cause ,GPI-Linked Proteins ,Transfection ,Biochemistry ,Madin Darby Canine Kidney Cells ,Viral Matrix Proteins ,03 medical and health sciences ,Dogs ,Influenza A Virus, H1N1 Subtype ,Viral envelope ,Interferon ,Antigens, CD ,Chlorocebus aethiops ,Influenza A virus ,medicine ,Viral neuraminidase ,Animals ,Humans ,Molecular Biology ,Vero Cells ,Virus Release ,Innate immune system ,Virion ,Cell Biology ,Virology ,Recombinant Proteins ,030104 developmental biology ,HEK293 Cells ,Gene Expression Regulation ,Host-Pathogen Interactions ,biology.protein ,Tetherin ,HIV-1 ,medicine.drug ,HeLa Cells ,Plasmids ,Signal Transduction - Abstract
BST-2 (tetherin, CD317, and HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In the present study, we report that BST-2 diminishes the production of IAV virus-like particles (VLPs) that are generated by viral neuraminidase and hemagglutinin proteins to a much greater degree than it inhibits the production of wild-type IAV particles. This relatively weaker inhibition of IAV is associated with reduction in BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to down-regulation of cell surface BST-2 via the proteasomal pathway. Similarly to the viral antagonist Vpu, M2 also rescues the production of human immunodeficiency virus-1 VLPs and IAV VLPs in the presence of BST-2. Replication of wild-type and the M2-deleted viruses were both inhibited by BST-2, with the M2-deleted IAV being more restricted. These data reveal one mechanism that IAV employs to counter restriction by BST-2.
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- 2016
8. Amphotericin B Inhibits Enterovirus 71 Replication by Impeding Viral Entry
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Shan Mei, Shan Cen, Jianwei Wang, Fengwen Xu, Lijuan Yin, Siqi Hu, Lili Ren, Qi Jin, Fei Guo, Zhendong Zhao, Chen Liang, Jian Li, Bin Ai, Ying Wang, Tingting Liu, and Xiaoxiao Zhao
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0301 basic medicine ,medicine.drug_class ,media_common.quotation_subject ,030106 microbiology ,Antibiotics ,Virus Replication ,Article ,Microbiology ,03 medical and health sciences ,Viral entry ,Amphotericin B ,Cell Line, Tumor ,Enterovirus Infections ,medicine ,Enterovirus 71 ,Humans ,Internalization ,media_common ,Multidisciplinary ,biology ,HEK 293 cells ,Virus Internalization ,biology.organism_classification ,Virology ,Enterovirus A, Human ,030104 developmental biology ,Viral replication ,Cell culture ,medicine.drug - Abstract
Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. There is thus an urgent need to find new treatments to control EV71 infection. In this study, we report potent inhibition of EV71 by a polyene antibiotic Amphotericin B. Amphotericin B profoundly diminished the expression of EV71 RNA and viral proteins in the RD cells and the HEK293 cells. As a result, EV71 production was inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1.75 μM in RD cells and 0.32 μM in 293 cells. In addition to EV71, EV68 was also strongly inhibited by Amphotericin B. Results of mechanistic studies revealed that Amphotericin B targeted the early stage of EV71 infection through impairing the attachment and internalization of EV71 by host cells. As an effective anti-fungi drug, Amphotericin B thus holds the promise of formulating a novel therapeutic to treat EV71 infection.
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- 2016
9. Characterization of the interactions between SIVrcm Vpx and red-capped mangabey SAMHD1
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Shan Mei, Fengwen Xu, Jinming Zhou, Qi Jin, Fei Guo, Chen Liang, Siqi Hu, Jian Li, Xiaoxiao Zhao, and Shan Cen
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Models, Molecular ,Cercocebus ,Protein Conformation ,Immunoblotting ,Biology ,medicine.disease_cause ,Biochemistry ,SAM Domain and HD Domain-Containing Protein 1 ,DDB1 ,Protein structure ,Ubiquitin ,Species Specificity ,medicine ,Animals ,Humans ,Immunoprecipitation ,Viral Regulatory and Accessory Proteins ,Mangabey ,Molecular Biology ,Monomeric GTP-Binding Proteins ,Ubiquitination ,Cell Biology ,Simian immunodeficiency virus ,biology.organism_classification ,Virology ,Ubiquitin ligase ,Proteolysis ,Sooty mangabey ,biology.protein ,Simian Immunodeficiency Virus ,SAMHD1 ,Protein Binding - Abstract
SAMHD1 (SAM domain- and HD domain-containing protein 1) inhibits HIV-1 infection of myeloid cells and resting CD4+ T-cells. Two lineages of primate lentiviruses, the sooty mangabey SIV (simian immunodeficiency virus) (SIVsm)/macaque SIV (SIVmac)/HIV-2 lineage and the red-capped mangabey SIV (SIVrcm) lineage, carry a SAMHD1 antagonist called Vpx. Vpx recognizes SAMHD1 and recruits a ubiquitin E3 ligase complex that is composed of CUL4 (Cullin4), DDB1 (damaged DNA-binding protein 1) and a member of the DCAF (DDB1/CUL4-associated factor) family called DCAF1. This E3 ligase complex polyubiquitinates SAMHD1, which leads to proteasomal degradation of SAMHD1. As opposed to the well-characterized interaction of SIVmac Vpx with human SAMHD1 and DCAF1, SIVrcm Vpx adopts a different mode of interaction with SAMHD1 of red-capped mangabeys. In the present study, we have characterized the interactions that are essential for SIVrcm Vpx-mediated degradation of rcmSAMHD1 (red-capped mangabey SAMHD1). Using mutagenesis and molecular modelling, we have determined the key role of the W23LHR26 peptide of SIVrcm Vpx in recognizing rcmSAMHD1. The amino acids Phe15, Leu36, Phe52, Arg55 and Arg56 at the N-terminal domain (NtD) of rcmSAMHD1 are involved in interaction with Vpxrcm (red-capped mangabey Vpx). The molecular model of rcmSAMHD1-NtD, Vpxrcm and C-terminal domain (CtD) of DCAF1 (DCAF1-CtD) complex reveals further that rcmSAMHD1-NtD and Vpxrcm utilize an interaction interface that is different from that used by human SAMHD1-CtD and Vpxsm. These findings provide further insights into the different modes of interaction between Vpx and SAMHD1 as the result of the ‘arms race’ of virus and host cell.
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- 2015
10. The interferon-induced MxB protein inhibits an early step of HIV-1 infection
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Fengwen Xu, Jin Qian, Chen Liang, Shan Cen, Shilei Ding, Zhenlong Liu, Fei Guo, Jinming Zhou, and Qinghua Pan
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biology ,business.industry ,RNA ,Virology ,Virus ,chemistry.chemical_compound ,Infectious Diseases ,Protein structure ,chemistry ,Interferon ,Poster Presentation ,biology.protein ,Medicine ,Antibody ,business ,Gene ,DNA ,Function (biology) ,medicine.drug - Abstract
Background Interferon protects cells from virus infection by inducing the expression of genes with antiviral activities. One such antiviral gene is Mx (myxovirus resistance) that was first identified in mice for its protection against influenza virus infection. Humans carry two Mx genes, MxA and MxB. Although MxA has been reported to inhibit a number of RNA and DNA viruses, the antiviral function of MxB has just begun to be revealed.
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- 2013
11. Identification of novel key amino acids at the interface of the transmembrane domains of human BST-2 and HIV-1 Vpu
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Jinming Zhou, Qi Jin, Shan Mei, Fengwen Xu, Siqi Hu, Shan Cen, Fei Guo, Jian Li, and Xiao-Jing Pang
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Bioluminescence Resonance Energy Transfer Techniques ,Models, Molecular ,animal diseases ,viruses ,Human Immunodeficiency Virus Proteins ,Human immunodeficiency virus type 1 ,Plasma protein binding ,Biology ,Molecular Dynamics Simulation ,medicine.disease_cause ,GPI-Linked Proteins ,Cell Line ,Protein structure ,Antigens, CD ,Virology ,Protein Interaction Mapping ,Vpu ,medicine ,Humans ,Viral Regulatory and Accessory Proteins ,chemistry.chemical_classification ,Mutation ,Research ,virus diseases ,BST-2 ,biochemical phenomena, metabolism, and nutrition ,Molecular biology ,Transmembrane protein ,Cell biology ,Amino acid ,Transmembrane domain ,Infectious Diseases ,chemistry ,Cell culture ,Tetherin ,Bioluminescence resonance energy transfer assay ,Protein Binding - Abstract
Background BST-2 (bone marrow stromal cell antigen 2) is an interferon-inducible protein that inhibits virus release by tethering viral particles to the cell surface. This antiviral activity of BST-2 is antagonized by HIV-1 accessory protein Vpu. Vpu physically interacts with BST-2 through their mutual transmembrane (TM) domains. In this study, we utilized the BRET assay and molecular dynamics (MD) simulation method to further characterize the interaction of BST-2 and Vpu. Results Amino acids I34, L37, P40 and L41 in the TM domain of BST-2, and L11, A18 and W22 in the TM domain of Vpu were identified to be critical for the interaction between BST-2 and Vpu. The residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu were shown, for the first time, to be important for their interaction. Furthermore, triple-amino-acid substitutions, 14–16 (AII to VAA) and 26–28 (IIE to AAA) in Vpu TM, not the single-residue mutation, profoundly disrupted BST-2/Vpu interaction. The results of MD simulation revealed significant conformational changes of the BST-2/Vpu complex as a result of mutating P40 of BST-2 and L11, 14–16 (AII to VAA) and 26–28 (IIE to AAA) of Vpu. In addition, disrupting the interaction between BST-2 and Vpu rendered BST-2 resistant to Vpu antagonization. Conclusions Through use of the BRET assay, we identified novel key residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu that are important for their interaction. These results add new insights into the molecular mechanism behind BST-2 antagonization by HIV-1 Vpu.
- Published
- 2013
12. IFP35 is involved in the antiviral function of interferon by association with the viral tas transactivator of bovine foamy virus
- Author
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Jian Wang, Qimin Chen, Yunqi Geng, Jun Zhou, Fengwen Xu, Yue Li, Wentao Qiao, and Juan Tan
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Gene Expression Regulation, Viral ,Immunology ,Cellular Response to Infection ,Microbiology ,Virus ,Cell Line ,Transactivation ,Interferon ,Transcription (biology) ,Virology ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Spumavirus ,Lung ,Cells, Cultured ,Regulation of gene expression ,biology ,Intracellular Signaling Peptides and Proteins ,RNA ,biology.organism_classification ,Virus Latency ,Viral replication ,Insect Science ,Trans-Activators ,Cattle ,Interferons ,medicine.drug - Abstract
Interferon-induced proteins (IFPs) exert multiple functions corresponding to diverse interferon signals. However, the intracellular functions of many IFPs are not fully characterized. Here, we report that IFP35, a member of the IFP family with a molecular mass of 35 kDa, can interact with the bovine Tas (BTas) regulatory protein of bovine foamy virus (BFV). The interaction involves NID2 (IFP35/Nmi homology domain) of IFP35 and the central domain of BTas. The overexpression of IFP35 disturbs the ability of BTas to activate viral-gene transcription and inhibits viral replication. The depletion of endogenous IFP35 by interfering RNA can promote the activation of BFV, suggesting an inhibitory function of IFP35 in viral-gene expression. In addition, IFP35 can interact with the homologous regulatory protein of prototype FV and arrest viral replication and repress viral transcription. Our study suggests that IFP35 may represent a novel pathway of interferon-mediated antiviral activity in host organisms that plays a role in the maintenance of FV latency.
- Published
- 2008
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