18 results on '"Fengwen Xu"'
Search Results
2. 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
3. IFITM3 Inhibits SARS-CoV-2 Infection and Is Associated with COVID-19 Susceptibility
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Fengwen Xu, Geng Wang, Fei Zhao, Yu Huang, Zhangling Fan, Shan Mei, Yu Xie, Liang Wei, Yamei Hu, Conghui Wang, Shan Cen, Chen Liang, Lili Ren, Fei Guo, and Jianwei Wang
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Infectious Diseases ,SARS-CoV-2 ,Virology ,Humans ,COVID-19 ,Membrane Proteins ,RNA-Binding Proteins ,Interferons ,Disease Susceptibility ,IFITM3 ,rs12252 ,Alleles - Abstract
SARS-CoV-2 has become a global threat to public health. Infected individuals can be asymptomatic or develop mild to severe symptoms, including pneumonia, respiratory distress, and death. This wide spectrum of clinical presentations of SARS-CoV-2 infection is believed in part due to the polymorphisms of key genetic factors in the population. In this study, we report that the interferon-induced antiviral factor IFITM3 inhibits SARS-CoV-2 infection by preventing SARS-CoV-2 spike-protein-mediated virus entry and cell-to-cell fusion. Analysis of a Chinese COVID-19 patient cohort demonstrates that the rs12252 CC genotype of IFITM3 is associated with SARS-CoV-2 infection risk in the studied cohort. These data suggest that individuals carrying the rs12252 C allele in the IFITM3 gene may be vulnerable to SARS-CoV-2 infection and thus may benefit from early medical intervention.
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- 2022
4. SERINC5 restricts influenza virus infectivity
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Fei Zhao, Fengwen Xu, Xiaoman Liu, Yamei Hu, Liang Wei, Zhangling Fan, Liming Wang, Yu Huang, Shan Mei, Li Guo, Long Yang, Shan Cen, Jianwei Wang, Chen Liang, and Fei Guo
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Immunology ,Orthomyxoviridae ,Antiviral Agents ,Microbiology ,Mice ,Hemagglutinins ,Virology ,Influenza, Human ,HIV-1 ,Genetics ,Animals ,Humans ,Parasitology ,nef Gene Products, Human Immunodeficiency Virus ,Molecular Biology ,Glycoproteins - Abstract
SERINC5 is a multi-span transmembrane protein that is incorporated into HIV-1 particles in producing cells and inhibits HIV-1 entry. Multiple retroviruses like HIV-1, equine infectious anemia virus and murine leukemia virus are subject to SERINC5 inhibition, while HIV-1 pseudotyped with envelope glycoproteins of vesicular stomatitis virus and Ebola virus are resistant to SERINC5. The antiviral spectrum and the underlying mechanisms of SERINC5 restriction are not completely understood. Here we show that SERINC5 inhibits influenza A virus infection by targeting virus-cell membrane fusion at an early step of infection. Further results show that different influenza hemagglutinin (HA) subtypes exhibit diverse sensitivities to SERINC5 restriction. Analysis of the amino acid sequences of influenza HA1 strains indicates that HA glycosylation sites correlate with the sensitivity of influenza HA to SERINC5, and the inhibitory effect of SERINC5 was lost when certain HA glycosylation sites were mutated. Our study not only expands the antiviral spectrum of SERINC5, but also reveals the role of viral envelope glycosylation in resisting SERINC5 restriction.
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- 2022
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. 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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8. 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
9. 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
10. 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
11. Identification of an endocytic signal essential for the antiviral action of IFITM3
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Fengwen Xu, Chen Liang, Shan-Lu Liu, Rui Jia, Wentao Qiao, Chunhui Miao, Jin Qian, Fei Guo, Yunfang Yao, Yunqi Geng, and Yi-Min Zheng
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Endosome ,Immunology ,Endocytic cycle ,Amino Acid Motifs ,Molecular Sequence Data ,Adaptor Protein Complex 2 ,Endosomes ,Biology ,Protein Sorting Signals ,Endocytosis ,Microbiology ,Article ,Influenza A Virus, H1N1 Subtype ,Viral entry ,Virology ,Humans ,Conserved Sequence ,Cell Membrane ,Membrane Proteins ,RNA-Binding Proteins ,Virus Internalization ,Transmembrane protein ,Transport protein ,Cell biology ,Adaptor Protein Complex mu Subunits ,Protein Subunits ,Protein Transport ,Endocytic vesicle ,HEK293 Cells ,Protein Binding - Abstract
Members of the interferon-induced transmembrane (IFITM) protein family inhibit the entry of a wide range of viruses. Viruses often exploit the endocytosis pathways to invade host cells and escape from the endocytic vesicles often in response to low pH. Localization to these endocytic vesicles is essential for IFITM3 to interfere with the cytosolic entry of pH-dependent viruses. However, the nature of the sorting signal that targets IFITM3 to these vesicles is poorly defined. In this study, we report that IFITM3 possesses a YxxΦ sorting motif, i.e., 20-YEML-23, that enables IFITM3 to undergo endocytosis through binding to the μ2 subunit of the AP-2 complex. IFITM3 accumulates at the plasma membrane as a result of either mutating 20-YEML-23, depleting the μ2 subunit, or overexpressing μ2 mutants. Importantly, blocking endocytosis of IFITM3 abrogates its ability to inhibit pH-dependent viruses. We have therefore identified a critical sorting signal, namely 20-YEML-23, that controls both the endocytic trafficking and the antiviral action of IFITM3. This finding also reveals that as an endocytic protein, IFITM3 first arrives at the plasma membrane before it is endocytosed and further traffics to the late endosomes where it acts to impede virus entry.
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- 2014
12. 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
13. 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
14. 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
15. IFP35 is involved in the antiviral function of interferon by association with the viral tas transactivator of bovine foamy virus
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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.
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- 2008
16. Lysine acetylation sites in bovine foamy virus transactivator BTas are important for its DNA binding activity
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Yunqi Geng, Juan Tan, Hongqi Han, Yue Li, Rui Chang, Wentao Qiao, and Fengwen Xu
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DNA Mutational Analysis ,p300 ,P300-CBP Transcription Factors ,Cell Line ,Bovine foamy virus ,Transactivation ,Viral Proteins ,Transcription (biology) ,Virology ,Cricetinae ,Animals ,Humans ,p300-CBP Transcription Factors ,Regulation of gene expression ,biology ,Lysine ,Promoter ,Acetylation ,Histone acetyltransferase ,DNA ,Molecular biology ,Long terminal repeat ,Amino Acid Substitution ,Host-Pathogen Interactions ,biology.protein ,Mutagenesis, Site-Directed ,Trans-Activators ,Spumavirus ,BTas ,Protein Binding - Abstract
Cellular acetylation signaling is important for viral gene regulation, particularly during the transactivation of retroviruses. The regulatory protein of bovine foamy virus (BFV), BTas, is a transactivator that augments viral gene transcription from both the long terminal repeat (LTR) promoter and the internal promoter (IP). In this study, we report that the histone acetyltransferase (HAT), p300, specifically acetylates BTas both in vivo and in vitro. Further studies demonstrated that BTas acetylation markedly enhances its transactivation activity. Mutagenesis analysis identified three lysines at positions 66, 109 and 110 in BTas that are acetylated by p300. The K110R mutant lost its binding to BFV promoter as well as its ability to activate BFV promoter. The acetylation of K66 and K109 may contribute to increased BTas binding ability. These results suggest that the p300-acetylated lysines of BTas are important for transactivation of BFV promoters and therefore have an important role in BFV replication.
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17. Dimerization of BTas is required for the transactivational activity of bovine foamy virus
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Fengwen Xu, Hongqi Han, Qimin Chen, Yunqi Geng, Wentao Qiao, and Juan Tan
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Homodimerization ,Bovine foamy virus ,Biology ,BFV ,Cell Line ,Viral Proteins ,Two-Hybrid System Techniques ,Virology ,Protein Interaction Mapping ,Humans ,Protein Interaction Domains and Motifs ,Promoter Regions, Genetic ,Sequence Deletion ,chemistry.chemical_classification ,Regulation of gene expression ,Functional analysis ,Terminal Repeat Sequences ,Promoter ,Molecular biology ,Long terminal repeat ,Amino acid ,Binding ability ,chemistry ,Spumavirus ,BTas ,Dimerization ,Function (biology) ,Transcription Factors - Abstract
The BTas protein of bovine foamy virus (BFV) is a 249-amino-acid nuclear regulatory protein which transactivates viral gene expression directed by the long terminal repeat promoter (LTR) and the internal promoter (IP). Here, we demonstrate the BTas protein forms a dimeric complex in mammalian cells by using mammalian two hybrid systems and cross-linking assay. Functional analyses with deletion mutants reveal that the region of 46–62aa is essential for dimer formation. Furthermore, our results show that deleting the dimerization region of BTas did not affect the localization of BTas, but that it did result in the loss of its transactivational activity on the LTR and IP. Furthermore, BTas (Δ46–62aa) retained binding ability to the LTR and IP similar to that of the wild-type BTas. These data suggest the dimerization region is necessary for the transactivational function of BTas and is crucial to the replication of BFV.
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18. 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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