The Experts below are selected from a list of 153 Experts worldwide ranked by ideXlab platform
Ian W Lipkin - One of the best experts on this subject based on the ideXlab platform.
-
z proteins of new world arenaViruses bind rig i and interfere with type i interferon induction
Journal of Virology, 2010Co-Authors: Thomas Briese, Ian W LipkinAbstract:The retinoic acid-inducible gene I product (RIG-I) is a cellular sensor of RNA Virus infection that regulates the cellular beta interferon (IFN-β) response. The nucleoproteins (NP) of arenaViruses are reported to antagonize the IFN response by inhibiting interferon regulatory factor 3 (IRF-3). Here, we demonstrate that the Z proteins of four New World (NW) arenaViruses, Guanarito Virus (GTOV), Junin Virus (JUNV), Machupo Virus (MAVC), and Sabia Virus (SABV), bind to RIG-I, resulting in downregulation of the IFN-β response. We show that expression of the four NW arenaVirus Z proteins inhibits IFN-β mRNA induction in A549 cells in response to RNA bearing 5′ phosphates (5′pppRNA). NW arenaVirus Z proteins interact with RIG-I in coimmunoprecipitation studies and colocalize with RIG-I. Furthermore, expression of Z proteins interferes with the interaction between RIG-I and MAVS. Z expression also impedes the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and IRF-3 activation. Our results indicate that NW arenaVirus Z proteins, but not Z protein of the Old World (OW) arenaVirus lymphocytic choriomeningitis Virus (LCMV) or Lassa Virus, bind to RIG-I and inhibit downstream activation of the RIG-I signaling pathway, preventing the transcriptional induction of IFN-β.
-
Z Proteins of New World ArenaViruses Bind RIG-I and Interfere with Type
2009Co-Authors: Interferon I Induction, Thomas Briese, Lina Fan, Ian W LipkinAbstract:The retinoic acid-inducible gene I product (RIG-I) is a cellular sensor of RNA Virus infection that regulates the cellular beta interferon (IFN-) response. The nucleoproteins (NP) of arenaViruses are reported to antagonize the IFN response by inhibiting interferon regulatory factor 3 (IRF-3). Here, we demonstrate that the Z proteins of four New World (NW) arenaViruses, Guanarito Virus (GTOV), Junin Virus (JUNV), Machupo Virus (MAVC), and Sabia Virus (SABV), bind to RIG-I, resulting in downregulation of the IFN- response. We show that expression of the four NW arenaVirus Z proteins inhibits IFN- mRNA induction in A549 cells in response to RNA bearing 5 phosphates (5pppRNA). NW arenaVirus Z proteins interact with RIG-I in coimmunoprecipitation studies and colocalize with RIG-I. Furthermore, expression of Z proteins interferes with the interaction between RIG-I and MAVS. Z expression also impedes the nuclear factor kappa light chain enhancer of activated B cells (NF-B) and IRF-3 activation. Our results indicate that NW arenaVirus Z proteins, but not Z protein of the Old World (OW) arenaVirus lymphocytic choriomeningitis Virus (LCMV) or Lassa Virus, bind to RIG-I and inhibit downstream activation of the RIG-I signaling pathway, preventing the transcriptional induction of IFN-. The innate immune system recognizes Virus infection and, as a first-line defense, induces antiviral responses by producin
Thomas Briese - One of the best experts on this subject based on the ideXlab platform.
-
z proteins of new world arenaViruses bind rig i and interfere with type i interferon induction
Journal of Virology, 2010Co-Authors: Thomas Briese, Ian W LipkinAbstract:The retinoic acid-inducible gene I product (RIG-I) is a cellular sensor of RNA Virus infection that regulates the cellular beta interferon (IFN-β) response. The nucleoproteins (NP) of arenaViruses are reported to antagonize the IFN response by inhibiting interferon regulatory factor 3 (IRF-3). Here, we demonstrate that the Z proteins of four New World (NW) arenaViruses, Guanarito Virus (GTOV), Junin Virus (JUNV), Machupo Virus (MAVC), and Sabia Virus (SABV), bind to RIG-I, resulting in downregulation of the IFN-β response. We show that expression of the four NW arenaVirus Z proteins inhibits IFN-β mRNA induction in A549 cells in response to RNA bearing 5′ phosphates (5′pppRNA). NW arenaVirus Z proteins interact with RIG-I in coimmunoprecipitation studies and colocalize with RIG-I. Furthermore, expression of Z proteins interferes with the interaction between RIG-I and MAVS. Z expression also impedes the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and IRF-3 activation. Our results indicate that NW arenaVirus Z proteins, but not Z protein of the Old World (OW) arenaVirus lymphocytic choriomeningitis Virus (LCMV) or Lassa Virus, bind to RIG-I and inhibit downstream activation of the RIG-I signaling pathway, preventing the transcriptional induction of IFN-β.
-
Z Proteins of New World ArenaViruses Bind RIG-I and Interfere with Type
2009Co-Authors: Interferon I Induction, Thomas Briese, Lina Fan, Ian W LipkinAbstract:The retinoic acid-inducible gene I product (RIG-I) is a cellular sensor of RNA Virus infection that regulates the cellular beta interferon (IFN-) response. The nucleoproteins (NP) of arenaViruses are reported to antagonize the IFN response by inhibiting interferon regulatory factor 3 (IRF-3). Here, we demonstrate that the Z proteins of four New World (NW) arenaViruses, Guanarito Virus (GTOV), Junin Virus (JUNV), Machupo Virus (MAVC), and Sabia Virus (SABV), bind to RIG-I, resulting in downregulation of the IFN- response. We show that expression of the four NW arenaVirus Z proteins inhibits IFN- mRNA induction in A549 cells in response to RNA bearing 5 phosphates (5pppRNA). NW arenaVirus Z proteins interact with RIG-I in coimmunoprecipitation studies and colocalize with RIG-I. Furthermore, expression of Z proteins interferes with the interaction between RIG-I and MAVS. Z expression also impedes the nuclear factor kappa light chain enhancer of activated B cells (NF-B) and IRF-3 activation. Our results indicate that NW arenaVirus Z proteins, but not Z protein of the Old World (OW) arenaVirus lymphocytic choriomeningitis Virus (LCMV) or Lassa Virus, bind to RIG-I and inhibit downstream activation of the RIG-I signaling pathway, preventing the transcriptional induction of IFN-. The innate immune system recognizes Virus infection and, as a first-line defense, induces antiviral responses by producin
Michael J. Buchmeier - One of the best experts on this subject based on the ideXlab platform.
-
Glycosylation site conservation and recombinant LCMV genetic stability.
2013Co-Authors: Cyrille J. Bonhomme, Kristeene A. Knopp, Lydia H. Bederka, Megan M. Angelini, Michael J. BuchmeierAbstract:Specific mutations of N-glycosylation sites were engineered to delete or add N-glycan on the LCM Virus glycoprotein.aConservation of the glycosylation site from alignment of arenaVirus GP sequences performed using CLC Sequence Viewer software. The 8 Old Word arenaViruses are: Lassa Virus (LASV), X52400; Ippy Virus (IPPYV), DQ328877; Mobala Virus (MOBV), AY342390; Mopeia Virus (MOPV), DQ328874; Morogoro Virus (MORV), EU914103; Dandenong Virus (DANV), EU136038; Lymphocytic choriomeningitis Virus (LCMV), AY847350; Lujo Virus (LUJV), FJ952384; while the 20 New World arenaViruses are: Pirital Virus (PIRV), AF277659; Allpahuayo Virus (ALLV), AY012687; Pichinde Virus (PICV), NC_006447, Parana Virus (PARV), AF512829; Flexal Virus (FLEV), AF512831; Oliveros Virus (OLVV), U34248; Latino Virus (LATV), AF512830; Machupo Virus (MACV), NC_005078; Junin Virus (JUNV), D10072; Tacaribe Virus (TCRV), NC_004293; Chapare Virus (CHAV), EU260463; Sabia Virus (SABV), NC_006317; Guanarito Virus (GTOV), NC_005077; Amapari Virus (AMAV), AF512834; Cupixi Virus (CPXV), AF512832; Skinner Tank Virus (SKTV), EU123328; Whitewater Arroyo Virus (WWAV), AF228063; Catarina Virus (CATV), DQ865245; Tamiami Virus (TAMV), AF512828; Bear Canyon Virus (BCNV), AF512833.bStability controlled by sequencing of GP for each rescued Virus mutant 72 h post infection in (i) epithelial cell lines: Vero E6 and HEK293T, (ii) neurons: cell line OBL21A and primary mouse cortical neuron, (iii) macrophages: cell line RAW264.7 and bone marrow derived macrophages. Stability was measured on a scale from 0–10 and represents the stability of the mutants during 10 passages, on epithelial cells, or during a 72 h infection, on primary cells. ‘0′ means no rLCMV rescued and ‘10′ mutation stable for more than 10 passages on epithelial cells and more than 72 h on primary cells.
-
A multivalent vaccination strategy for the prevention of Old World arenaVirus infection in humans.
Journal of Virology, 2010Co-Authors: Jason Botten, J. Lindsay Whitton, Polly Barrowman, John Sidney, Jason K. Whitmire, Jeff Alexander, Maya F. Kotturi, Alessandro Sette, Michael J. BuchmeierAbstract:ArenaViruses cause severe human disease ranging from aseptic meningitis following lymphocytic choriomeningitis Virus (LCMV) infection to hemorrhagic fever syndromes following infection with Guanarito Virus (GTOV), Junin Virus (JUNV), Lassa Virus (LASV), Machupo Virus (MACV), Sabia Virus (SABV), or Whitewater Arroyo Virus (WWAV). Cellular immunity, chiefly the CD8 T-cell response, plays a critical role in providing protective immunity following infection with the Old World arenaViruses LASV and LCMV. In the current study, we evaluated whether HLA class I-restricted epitopes that are cross-reactive among pathogenic arenaViruses could be identified for the purpose of developing an epitope-based vaccination approach that would cross-protect against multiple arenaViruses. We were able to identify a panel of HLA-A*0201-restricted peptides derived from the same region of the glycoprotein precursor (GPC) of LASV (GPC spanning residues 441 to 449 [GPC441-449]), LCMV (GPC447-455), JUNV (GPC429-437), MACV (GPC444-452), GTOV (GPC427-435), and WWAV (GPC428-436) that displayed high-affinity binding to HLA-A*0201 and were recognized by CD8 T cells in a cross-reactive manner following LCMV infection or peptide immunization of HLA-A*0201 transgenic mice. Immunization of HLA-A*0201 mice with the Old World peptide LASV GPC441-449 or LCMV GPC447-455 induced high-avidity CD8 T-cell responses that were able to kill syngeneic target cells pulsed with either LASV GPC441-449 or LCMV GPC447-455 in vivo and provided significant protection against viral challenge with LCMV. Through this study, we have demonstrated that HLA class I-restricted, cross-reactive epitopes exist among diverse arenaViruses and that individual epitopes can be utilized as effective vaccine determinants for multiple pathogenic arenaViruses. ArenaViruses are a family of rodent-borne Viruses that are associated with severe disease in humans. Phylogenetically, the arenaViruses are organized into Old World or New World groups, with a subdivision of the New World Viruses falling into three distinct lineages (A to C) (17). At least eight arenaViruses are known to cause human disease. Of the New World Viruses, Junin Virus (JUNV), Machupo Virus (MACV), Guanarito Virus (GTOV), and Sabia Virus (SABV) (all members of lineage B) are etiologic agents of hemorrhagic fever syndromes in South
Jay W. Hooper - One of the best experts on this subject based on the ideXlab platform.
-
Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever
Journal of Virology, 2016Co-Authors: Joseph W. Golden, Piet Maes, Steven A. Kwilas, John Ballantyne, Jay W. HooperAbstract:UNLABELLED Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaViruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaViruses. In the present study, we produced arenaVirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junin Virus (JUNV), Machupo Virus (MACV), and Guanarito Virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT(50)), exceeded 5,000 against homologous Viruses. Antisera against each targeted Virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia Virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenaVirus immunotherapeutic. IMPORTANCE ArenaViruses are an important family of emerging Viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can mitigate the severity of disease caused by arenaViruses, particularly species found in South America. Because of variations in potency of the human-derived product, limited availability, and safety concerns, this treatment option has essentially been abandoned. Accordingly, despite this approach being an effective postinfection treatment option, research on novel approaches to produce potent polyclonal antibody-based therapies have been deficient. Here we show that DNA-based vaccine technology can be used to make potently neutralizing antibodies in rabbits that exclusively target the glycoproteins of several human-pathogenic arenaViruses found in South America, including JUNV, MACV, GTOV, and SABV. These antibodies protected guinea pigs from lethal disease when given post-Virus challenge. We also generated a purified antibody cocktail with antibodies targeting three arenaViruses and demonstrated protective efficacy against all three targets. Our findings demonstrate that use of the DNA vaccine technology could be used to produce candidate antiarenaVirus neutralizing antibody-based products.
Hooper, Jay W - One of the best experts on this subject based on the ideXlab platform.
-
Glycoprotein-specific antibodies produced by DNA vaccination protect guinea pigs from lethal Argentine and Venezuelan hemorrhagic fever
'American Society for Microbiology', 2016Co-Authors: Golden, Joseph W, Maes Piet, Kwilas, Steven A, Ballantyne John, Hooper, Jay WAbstract:Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaViruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaViruses. In the present study, we produced arenaVirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín Virus (JUNV), Machupo Virus (MACV), and Guanarito Virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT50), exceeded 5,000 against homologous Viruses. Antisera against each targeted Virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia Virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenaVirus immunotherapeutic.status: publishe
