10 results on '"Fengwen Xu"'
Search Results
2. The Engineered MARCH8-Resistant Vesicular Stomatitis Virus Glycoprotein Enhances Lentiviral Vector Transduction
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Hong Sun, Di Zhang, Fei Zhao, Shan Mei, Chen Liang, Liang Wei, Fei Guo, Jianwei Wang, Xiaoman Liu, Shan Cen, Zhangling Fan, Fengwen Xu, Li Guo, Yu Huang, and Siqi Hu
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viruses ,Genetic enhancement ,Genetic Vectors ,Mutant ,Virus ,Viral vector ,03 medical and health sciences ,Transduction (genetics) ,0302 clinical medicine ,Viral Envelope Proteins ,Ubiquitin ,Transduction, Genetic ,Genetics ,Animals ,Molecular Biology ,Glycoproteins ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Lentivirus ,Genetic Therapy ,biology.organism_classification ,Ubiquitin ligase ,Cell biology ,Vesicular stomatitis virus ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Vesicular Stomatitis - Abstract
Lentiviral vectors are one of the most commonly used viral delivery systems for gene therapy. Vesicular stomatitis virus-G envelope glycoprotein (VSV G)-pseudotyped lentiviral vectors have been widely used in clinical studies for treatment of virus infections and genetic deficient diseases. However, the efficiency of lentiviral vector transduction has been long recognized as a limiting factor in clinical gene therapy application, especially in transducing hematopoietic stem cells. MARCH8 (membrane-associated RING-CH 8), an E3 ubiquitin ligase, has been reported to target and downregulate VSV G. Results in this study show that MARCH8 induces ubiquitination and lysosome degradation of VSV G, and knockout of MARCH8 in virus-producing cells increases lentiviral vector transduction by elevating the level of VSV G protein. We then engineered VSV G mutant that has the lysine residues in the cytoplasmic domain substituted for arginine, and showed that this G mutant resists degradation by MARCH8, and allows the enhancement of transduction efficiency of lentiviral vector particles than the parental VSV G protein. This engineered VSV G mutant thus further advances the lentiviral vector system as a powerful tool in gene therapy.
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- 2021
3. 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 ...
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- 2020
4. CRISPR-Cas13a Inhibits HIV-1 Infection
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Fei Zhao, Chen Liang, Liang Wei, Fei Guo, Fengwen Xu, Yu Huang, Siqi Hu, Shan Mei, Weijun Zhu, Lijuan Yin, Shan Cen, Di Zhang, Hong Sun, Zhen Wang, and Xiaoman Liu
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0301 basic medicine ,Effector ,viruses ,lcsh:RM1-950 ,RNA ,Transfection ,RNA Phages ,Biology ,Virology ,Article ,3. Good health ,03 medical and health sciences ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,0302 clinical medicine ,Genome editing ,Capsid ,Immunity ,030220 oncology & carcinogenesis ,Drug Discovery ,Molecular Medicine ,CRISPR - Abstract
CRISPR-Cas provides bacteria and archaea with immunity against invading phages and foreign plasmid DNA and has been successfully adapted for gene editing in a variety of species. The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Here we report the repurposing of CRISPR-Cas13a to inhibit human immunodeficiency virus type 1 (HIV-1) infection through targeting HIV-1 RNA and diminishing viral gene expression. We observed strong inhibition of HIV-1 infection by CRISPR-Cas13a in human cells. We showed that CRISPR-Cas13a not only diminishes the level of newly synthesized viral RNA, either from the transfected plasmid DNA or from the viral DNA, which is integrated into cellular DNA, but it also targets and destroys the viral RNA that enters cells within viral capsid, leading to strong inhibition of HIV-1 infection. Together, our results suggest that CRISPR-Cas13a provides a potential novel tool to treat viral diseases in humans., Graphical Abstract, The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Yin et al. demonstrate that CRISPR-Cas13a targets and cleaves the HIV RNA genome and mRNA, leading to strong inhibition of HIV-1 infection.
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- 2020
5. 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
6. 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
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. 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.
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- 2013
9. Tetherin inhibits prototypic foamy virus release
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Yunqi Geng, Dan Xu, Yue Li, Fengwen Xu, Chen Liang, Wentao Qiao, Ruikang Liu, and Juan Tan
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Glycosylation ,viruses ,Human Immunodeficiency Virus Proteins ,Mutant ,GPI-Linked Proteins ,lcsh:Infectious and parasitic diseases ,chemistry.chemical_compound ,Dogs ,Viral envelope ,Antigens, CD ,Virology ,Animals ,Humans ,Viral Regulatory and Accessory Proteins ,lcsh:RC109-216 ,Spumavirus ,Virus Release ,biology ,Research ,Wild type ,Haplorhini ,biology.organism_classification ,Protein Structure, Tertiary ,Transmembrane domain ,Infectious Diseases ,chemistry ,Host-Pathogen Interactions ,HIV-1 ,Tetherin ,Cattle ,Protein Multimerization - Abstract
Background Tetherin (also known as BST-2, CD317, and HM1.24) is an interferon- induced protein that blocks the release of a variety of enveloped viruses, such as retroviruses, filoviruses and herpesviruses. However, the relationship between tetherin and foamy viruses has not been clearly demonstrated. Results In this study, we found that tetherin of human, simian, bovine or canine origin inhibits the production of infectious prototypic foamy virus (PFV). The inhibition of PFV by human tetherin is counteracted by human immunodeficiency virus type 1 (HIV-1) Vpu. Furthermore, we generated human tetherin transmembrane domain deletion mutant (delTM), glycosyl phosphatidylinositol (GPI) anchor deletion mutant (delGPI), and dimerization and glycosylation deficient mutants. Compared with wild type tetherin, the delTM and delGPI mutants only moderately inhibited PFV production. In contrast, the dimerization and glycosylation deficient mutants inhibit PFV production as efficiently as the wild type tetherin. Conclusions These results demonstrate that tetherin inhibits the release and infectivity of PFV, and this inhibition is antagonized by HIV-1 Vpu. Both the transmembrane domain and the GPI anchor of tetherin are important for the inhibition of PFV, whereas the dimerization and the glycosylation of tetherin are dispensable.
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- 2011
10. BoHV-4 immediate early 1 gene is a dispensable gene and its product is not a bone marrow stromal cell antigen 2 counteracting factor
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Wentao Qiao, Valentina Franceschi, Sandro Cavirani, Gaetano Donofrio, Fengwen Xu, Sarah Jacca, Antonio Capocefalo, and Alfonso Rosamilia
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Gene Expression Regulation, Viral ,Chromosomes, Artificial, Bacterial ,Genome evolution ,viruses ,Bacteria artificial chromosome ,Genome, Viral ,Viral Plaque Assay ,Biology ,Gene delivery ,Virus Replication ,Gene dosage ,Cell Line ,Viral vector ,Immediate early gene ,Gene product ,Gene knock-down ,Animals ,Humans ,Bovine herpesvirus 4 ,Genes, Immediate-Early ,Gene ,Regulation of gene expression ,General Veterinary ,virus diseases ,Mesenchymal Stem Cells ,General Medicine ,Virology ,veterinary(all) ,Herpesvirus 4, Bovine ,Viral replication ,Impaired viral replication ,Gene Deletion ,Research Article - Abstract
Background Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus whose genome was cloned as Bacterial Artificial Chromosome (BAC) and exploited as a gene delivery vector for vaccine purposes. Although BoHV-4 genome has been completely sequenced and its open reading frames (ORFs) structurally defined in silico, most of them are not functionally characterized. In BoHV-4 genome two major immediate early genes (IE) are present, IE1 and IE2. IE2 is an essential gene because its removal from the viral genome renders the virus unable to replicate, whereas for IE1 no many functional information are available. Results In this work, IE1 contribution in initiating and maintaining BoHV-4 lytic replication was assessed generating a recombinant BoHV-4 genome lacking of IE1 gene, BoHV-4ΔIE1. In contrast to BoHV-4IE2 deleted mutant, BoHV-4ΔIE1 infectious replicating viral particles (IRVPs) could be reconstituted following viral DNA electroporation in permissive cells. However the titer of BoHV-4ΔIE1 IRVPs produced into the cell supernatant and BoHV-4ΔIE1 plaques size were reduced respect to BoHV-4 undeleted control. Further the impaired BoHV-4ΔIE1 IRVPs produced into the cell supernatant could be rescued by expressing IE1 gene product in trans, confirming the implication of IE1 in BoHV-4 lytic replication. Next, the possible role of BoHV-4IE1 as bone marrow stromal cell antigen 2 (BST-2) counteracting factor, as hypothesized by IE1 amino-terminal gene product homology with Kaposi Sarcoma Associated Herpesvirus (KSHV) K5, was excluded too. Conclusions Although the real function of BoHV-4IE1 is still elusive, a new BoHV-4 genome gene locus as a target site for the insertion of foreign DNA and resulting in the attenuation of the virus has been revealed. These data can be considered of relevance to improve BoHV-4 gene delivery properties. Electronic supplementary material The online version of this article (doi:10.1186/s12917-015-0540-4) contains supplementary material, which is available to authorized users.
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