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Dennis H. Bamford - One of the best experts on this subject based on the ideXlab platform.

  • A Structural Model of the Genome Packaging Process in a Membrane-Containing Double Stranded DNA Virus
    PLoS biology, 2014
    Co-Authors: Chuan Hong, Dennis H. Bamford, Hanna M. Oksanen, Xiangan Liu, Joanita Jakana, Wah Chiu
    Abstract:

    Two crucial steps in the Virus life cycle are genome encapsidation to form an infective virion and genome exit to infect the next host cell. In most icosahedral Double-Stranded (ds) DNA Viruses, the viral genome enters and exits the capsid through a unique vertex. Internal membrane-containing Viruses possess additional complexity as the genome must be translocated through the viral membrane bilayer. Here, we report the structure of the genome packaging complex with a membrane conduit essential for viral genome encapsidation in the tailless icosahedral membrane-containing bacteriophage PRD1. We utilize single particle electron cryo-microscopy (cryo-EM) and symmetry-free image reconstruction to determine structures of PRD1 virion, procapsid, and packaging deficient mutant particles. At the unique vertex of PRD1, the packaging complex replaces the regular 5-fold structure and crosses the lipid bilayer. These structures reveal that the packaging ATPase P9 and the packaging efficiency factor P6 form a dodecameric portal complex external to the membrane moiety, surrounded by ten major capsid protein P3 trimers. The viral transmembrane density at the special vertex is assigned to be a hexamer of heterodimer of proteins P20 and P22. The hexamer functions as a membrane conduit for the DNA and as a nucleating site for the unique vertex assembly. Our structures show a conformational alteration in the lipid membrane after the P9 and P6 are recruited to the virion. The P8-genome complex is then packaged into the procapsid through the unique vertex while the genome terminal protein P8 functions as a valve that closes the channel once the genome is inside. Comparing mature virion, procapsid, and mutant particle structures led us to propose an assembly pathway for the genome packaging apparatus in the PRD1 virion.

  • A minor capsid protein P30 is essential for bacteriophage PRD1 capsid assembly.
    Journal of molecular biology, 2001
    Co-Authors: Pia S. Rydman, Jaana K. H. Bamford, Dennis H. Bamford
    Abstract:

    Bacteriophage PRD1 is a Double-Stranded DNA Virus infecting Gram-negative hosts. It has a membrane component located in the interior of the isometric capsid. In addition to the major capsid protein P3, the capsid contains a 9 kDa protein P30. Protein P30 is proposed to be located between the adjacent facets of the icosahedral capsid and is required for stable capsid assembly. In its absence, an empty phage-specific membrane vesicle is formed. The major protein component of this vesicle is a phage-encoded assembly factor, protein P10, that is not present in the final structure.

  • Bacteriophage PRD1 proteins: cross-linking and scanning transmission electron microscopy analysis.
    Virology, 1993
    Co-Authors: Cheng Luo, Jarkko Hantula, Willem Tichelaar, Dennis H. Bamford
    Abstract:

    Abstract Bacteriopbage PRD1, a Double-Stranded DNA Virus infecting Escherichia coli, has a membrane inside the protein capsid. Chemical cross-linking and scanning transmission electron microscopy showed that the multimeric major coat protein (P3) exists in a trimeric form. Cross-linking revealed, in addition, that protein P11, located between the protein coat and the membrane, exists also as a homotrimer. Minor protein P7 was associated with the major coat protein P3. Under nonreducing conditions the infectivity proteins P16 and P18 formed homomultimeric complexes which were dissociated upon addition of 2-mercaptoethanol.

  • Binding of an Escherichia coli Double-Stranded DNA Virus PRD1 to a receptor coded by an IncP-type plasmid.
    Journal of bacteriology, 1993
    Co-Authors: Mika M. Kotilainen, Jaana K. H. Bamford, A. M. Grahn, Dennis H. Bamford
    Abstract:

    IncP plasmid RP1 Tra regions are needed to assemble the receptor for lipid-containing Double-Stranded DNA bacteriophage PRD1 on the cell surface. Using radioactively labeled phage and electron microscopic techniques, we showed that the surfaces of Salmonella typhimurium(RP1) and Escherichia coli(RP1) cells contained approximately 50 and 20 PRD1 binding sites, respectively. Expression of the receptor was growth phase dependent and was highest at late logarithmic or early stationary phase. The PRD1-resistant RP1 transposon mutants isolated were all Tra-, and the transposons were located in both the Tra1 and Tra2 regions. Images

Dmitry M Shayakhmetov - One of the best experts on this subject based on the ideXlab platform.

  • Virus binding to a plasma membrane receptor triggers interleukin 1α mediated proinflammatory macrophage response in vivo
    Immunity, 2009
    Co-Authors: Nelson C Di Paolo, Kaja Muralikrishna, Alan Aderem, Edward A Miao, Richard A Flavell, Thalia Papayannopoulou, Yoichiro Iwakura, Dmitry M Shayakhmetov
    Abstract:

    Summary The recognition of viral components by host pattern-recognition receptors triggers the induction of the antiviral innate immune response. Toll-like receptor 9 (TLR9) and NLRP3 inflammasome were shown to be the principal specific sensors of viral Double-Stranded DNA. Here we present evidence that macrophages in vivo activated an innate immune response to a Double-Stranded DNA Virus, adenoVirus (Ad), independently of TLR9 or NLRP3 inflammasome. In response to Ad, macrophage-derived IL-1α triggered IL-1RI-dependent production of a defined set of proinflammatory cytokines and chemokines. The IL-1α-mediated response required a selective interaction of Virus arginine-glycine-aspartic acid (RGD) motifs with macrophage β 3 integrins. Thus, these data identify IL-1α-IL-1RI as a key pathway allowing for the activation of proinflammatory responses to the Virus, independently of its genomic nucleic acid recognition.

  • Virus binding to a plasma membrane receptor triggers interleukin 1α mediated proinflammatory macrophage response in vivo
    Immunity, 2009
    Co-Authors: Nelson C Di Paolo, Kaja Muralikrishna, Alan Aderem, Edward A Miao, Richard A Flavell, Thalia Papayannopoulou, Yoichiro Iwakura, Dmitry M Shayakhmetov
    Abstract:

    The recognition of viral components by host pattern-recognition receptors triggers the induction of the antiviral innate immune response. Toll-like receptor 9 (TLR9) and NLRP3 inflammasome were shown to be the principal specific sensors of viral Double-Stranded DNA. Here we present evidence that macrophages in vivo activated an innate immune response to a Double-Stranded DNA Virus, adenoVirus (Ad), independently of TLR9 or NLRP3 inflammasome. In response to Ad, macrophage-derived IL-1 alpha triggered IL-1RI-dependent production of a defined set of proinflammatory cytokines and chemokines. The IL-1 alpha-mediated response required a selective interaction of Virus arginine-glycine-aspartic acid (RGD) motifs with macrophage beta(3) integrins. Thus, these data identify IL-1 alpha-IL-1RI as a key pathway allowing for the activation of proinflammatory responses to the Virus, independently of its genomic nucleic acid recognition.

Jason W. Upton - One of the best experts on this subject based on the ideXlab platform.

  • Murine cytomegaloVirus IE3-dependent transcription is required for DAI/ZBP1-mediated necroptosis
    EMBO reports, 2017
    Co-Authors: Haripriya Sridharan, Katherine B Ragan, Hongyan Guo, Ryan P. Gilley, Vanessa J Landsteiner, William J. Kaiser, Jason W. Upton
    Abstract:

    DNA-dependent activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) is a crucial sensor of necroptotic cell death induced by murine cytomegaloVirus (MCMV) in its natural host. Here, we show that viral capsid transport to the nucleus and subsequent viral IE3-dependent early transcription are required for necroptosis. Necroptosis induction does not depend on input virion DNA or newly synthesized viral DNA A putative RNA-binding domain of DAI/ZBP1, Zα2, is required to sense Virus and trigger necroptosis. Thus, MCMV IE3-dependent transcription from the viral genome plays a crucial role in activating DAI/ZBP1-dependent necroptosis. This implicates RNA transcripts generated by a large Double-Stranded DNA Virus as a biologically relevant ligand for DAI/ZBP1 during natural viral infection.

  • murine cytomegaloVirus ie3 dependent transcription is required for dai zbp1 mediated necroptosis
    EMBO Reports, 2017
    Co-Authors: Haripriya Sridharan, Katherine B Ragan, Hongyan Guo, Ryan P. Gilley, Vanessa J Landsteiner, William J. Kaiser, Jason W. Upton
    Abstract:

    DNA-dependent activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) is a crucial sensor of necroptotic cell death induced by murine cytomegaloVirus (MCMV) in its natural host. Here, we show that viral capsid transport to the nucleus and subsequent viral IE3-dependent early transcription are required for necroptosis. Necroptosis induction does not depend on input virion DNA or newly synthesized viral DNA A putative RNA-binding domain of DAI/ZBP1, Zα2, is required to sense Virus and trigger necroptosis. Thus, MCMV IE3-dependent transcription from the viral genome plays a crucial role in activating DAI/ZBP1-dependent necroptosis. This implicates RNA transcripts generated by a large Double-Stranded DNA Virus as a biologically relevant ligand for DAI/ZBP1 during natural viral infection.

Jeffrey I Cohen - One of the best experts on this subject based on the ideXlab platform.

  • update on new antivirals under development for the treatment of double stranded DNA Virus infections
    Clinical Pharmacology & Therapeutics, 2010
    Co-Authors: Lesia K Dropulic, Jeffrey I Cohen
    Abstract:

    All of the currently available antiviral agents used to treat Double-Stranded (ds) DNA Viruses inhibit the same target, the viral DNA polymerase, with the exception of interferon-α. With increasing reports of the development of resistance of herpes simplex Virus, cytomegaloVirus, and hepatitis B Virus to some of these drugs, new antiviral agents are needed for these infections. Additionally, no drugs are approved to treat several DNA Virus infections including those caused by adenoVirus, smallpox, molluscum contagiosum, and BK Virus. We report on the status of 10 new antiviral drugs for the treatment of dsDNA Viruses. CMX-001 has broad activity against dsDNA Viruses; 3 helicase-primase inhibitors, marabavir, and FV-100 have activity against certain herpesViruses; ST-246 inhibits poxViruses; GS-9191 inhibits papillomaViruses; and clevudine and emtricitabine are active against hepatitis B Virus. Most of these drugs have completed at least phase I trials in humans and several are in additional clinical trials.

  • Update on New Antivirals Under Development for the Treatment of Double‐Stranded DNA Virus Infections
    Clinical Pharmacology & Therapeutics, 2010
    Co-Authors: Lesia K Dropulic, Jeffrey I Cohen
    Abstract:

    All of the currently available antiviral agents used to treat Double-Stranded (ds) DNA Viruses inhibit the same target, the viral DNA polymerase, with the exception of interferon-α. With increasing reports of the development of resistance of herpes simplex Virus, cytomegaloVirus, and hepatitis B Virus to some of these drugs, new antiviral agents are needed for these infections. Additionally, no drugs are approved to treat several DNA Virus infections including those caused by adenoVirus, smallpox, molluscum contagiosum, and BK Virus. We report on the status of 10 new antiviral drugs for the treatment of dsDNA Viruses. CMX-001 has broad activity against dsDNA Viruses; 3 helicase-primase inhibitors, marabavir, and FV-100 have activity against certain herpesViruses; ST-246 inhibits poxViruses; GS-9191 inhibits papillomaViruses; and clevudine and emtricitabine are active against hepatitis B Virus. Most of these drugs have completed at least phase I trials in humans and several are in additional clinical trials.

Yong Kuk Kwon - One of the best experts on this subject based on the ideXlab platform.

  • development of a highly sensitive single tube nested pcr protocol directed toward the sequence of virion envelope proteins for detection of white spot syndrome Virus infection improvement of pcr methods for detection of wssv
    Aquaculture, 2013
    Co-Authors: Ji Young Park, Kwang Il Kim, Seong Jun Joh, Ja Young Kang, Jun Hun Kwon, Hee Soo Lee, Yong Kuk Kwon
    Abstract:

    Abstract White spot syndrome Virus (WSSV) is a Double-Stranded DNA Virus that causes severe mortality, leading to great economic loss for cultured shrimp farms. The Manual for Aquatic Animals published by the Office International des Epizooties (OIE, 2012) announced the nested PCR protocol, developed by Lo et al. in 1996 as the standard protocol for WSSV diagnosis. Because current detection tools are prone to carryover contamination and are labor-intensive, an accurate and convenient technique is required. Therefore, the aim of this study was to develop an improved diagnostic PCR method for WSSV that overcomes the known drawbacks of the conventional PCR method. We designed primers directed toward the nucleotide sequence encoding envelope proteins of WSSV, VP19 and VP28. By applying an antisense oligonucleotide technique, we converted this PCR assay into a non-stop one-tube system, subsequently enabling a faster and more sensible PCR assay. In practice, the newly developed protocol detected the WSSV genome from imported frozen shrimps, crabs and bivalves, with a shorter PCR running time and a higher sensitivity compared with other PCR methods.