The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
Ashley M. Grant - One of the best experts on this subject based on the ideXlab platform.
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Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo characterization in Interferon (αβ/γ) Receptor double knockout mice
Journal of virology, 2013Co-Authors: Michael Patterson, Alexey Seregin, Cheng Huang, Olga A. Kolokoltsova, Jennifer K. Smith, Milagros Miller, Jeanon N. Smith, Nadezhda E. Yun, Allison Poussard, Ashley M. GrantAbstract:Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and Gamma Interferon Receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.
Michael Patterson - One of the best experts on this subject based on the ideXlab platform.
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Rescue of a Recombinant Machupo Virus from Cloned cDNAs and In Vivo Characterization in Interferon (/) Receptor Double Knockout Mice
2016Co-Authors: Michael Patterson, Alexey Seregin, Cheng Huang, Olga A. Kolokoltsova, Milagros Miller, Allison Poussard, Jennifer Smith, Jeanon Smith, Nadezhda Yun, Ashley GrantAbstract:Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical dis-ease associated with highmortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and Gamma Interferon Receptor knockout mice, including neurological disease development and highmortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates. Amember of the family Arenaviridae, Machupo virus (MACV)is an enveloped, bisegmented negative-stranded RNA virus. Arenaviruses utilize an ambisense coding strategy to direct viral gene transcription from two genomic segments, the large segment (L, ca. 7.2 kb) and the small segment (S, ca. 3.3 kb). Each segment carries two viral genes; S encodes the glycoprotein precursor (GPC) and the nucleoprotein (NP), while L encodes the RNA-dependent RNA polymerase (L polymerase) and the small RING finger protein Z. The GPC is posttranslationally cleaved by th
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Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo characterization in Interferon (αβ/γ) Receptor double knockout mice
Journal of virology, 2013Co-Authors: Michael Patterson, Alexey Seregin, Cheng Huang, Olga A. Kolokoltsova, Jennifer K. Smith, Milagros Miller, Jeanon N. Smith, Nadezhda E. Yun, Allison Poussard, Ashley M. GrantAbstract:Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and Gamma Interferon Receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.
Michael G Katze - One of the best experts on this subject based on the ideXlab platform.
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the alpha beta Interferon Receptor provides protection against influenza virus replication but is dispensable for inflammatory response signaling
Journal of Virology, 2010Co-Authors: Alan G. Goodman, Sean C. Proll, Cristian Cilloniz, Victoria S. Carter, Terrence M Tumpey, Marcus J. Korth, Xinxia Peng, Hui Zeng, Michael G KatzeAbstract:The innate immune response provides the first line of defense against foreign pathogens by responding to molecules that are a signature of a pathogenic infection. Certain RNA viruses, such as influenza virus, produce double-stranded RNA as an intermediate during the replication life cycle, which activates pathogen recognition Receptors capable of inducing Interferon production. By engaging Interferon Receptors, Interferon activates the JAK-STAT pathway and results in the positive feedback of Interferon production, amplifying the response to viral infection. To examine how deficiencies in Interferon signaling affect the cellular response to infection, we performed influenza virus infections of mouse embryonic fibroblasts lacking the alpha/beta Interferon Receptor, the Gamma Interferon Receptor, or both. In the absence of the alpha/beta Interferon Receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-κB; the presence or absence of the Gamma Interferon Receptor did not exhibit discernible differences in these readouts. Analysis of gene expression profiles showed that while cells lacking the alpha/beta Interferon Receptor exhibited decreased levels of transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to levels similar to those of cells containing the Receptor. These results indicate that while the alpha/beta Interferon Receptor is needed to curb viral replication, it is dispensable for the induction of certain inflammatory and apoptotic genes. We have identified potential pathways, via Interferon regulatory factor 3 (IRF3) activation or Hoxa13 , Polr2a , Nr4a1 , or Ing1 induction, that contribute to this redundancy. This study illustrates another way in which the host has evolved to establish several overlapping mechanisms to respond to viral infections.
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The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication but Is Dispensable for Inflammatory Response Signaling
Journal of Virology, 2009Co-Authors: Alan G. Goodman, Sean C. Proll, Cristian Cilloniz, Victoria S. Carter, Terrence M Tumpey, Marcus J. Korth, Xinxia Peng, Hui Zeng, Michael G KatzeAbstract:The innate immune response provides the first line of defense against foreign pathogens by responding to molecules that are a signature of a pathogenic infection. Certain RNA viruses, such as influenza virus, produce double-stranded RNA as an intermediate during the replication life cycle, which activates pathogen recognition Receptors capable of inducing Interferon production. By engaging Interferon Receptors, Interferon activates the JAK-STAT pathway and results in the positive feedback of Interferon production, amplifying the response to viral infection. To examine how deficiencies in Interferon signaling affect the cellular response to infection, we performed influenza virus infections of mouse embryonic fibroblasts lacking the alpha/beta Interferon Receptor, the Gamma Interferon Receptor, or both. In the absence of the alpha/beta Interferon Receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-κB; the presence or absence of the Gamma Interferon Receptor did not exhibit discernible differences in these readouts. Analysis of gene expression profiles showed that while cells lacking the alpha/beta Interferon Receptor exhibited decreased levels of transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to levels similar to those of cells containing the Receptor. These results indicate that while the alpha/beta Interferon Receptor is needed to curb viral replication, it is dispensable for the induction of certain inflammatory and apoptotic genes. We have identified potential pathways, via Interferon regulatory factor 3 (IRF3) activation or Hoxa13 , Polr2a , Nr4a1 , or Ing1 induction, that contribute to this redundancy. This study illustrates another way in which the host has evolved to establish several overlapping mechanisms to respond to viral infections.
Candido Juarez - One of the best experts on this subject based on the ideXlab platform.
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staphylococcal enterotoxin b in vivo modulates both Gamma Interferon Receptor expression and ligand induced activation of signal transducer and activator of transcription 1 in t cells
Infection and Immunity, 2007Co-Authors: R Plaza, J L Rodriguezsanchez, Candido JuarezAbstract:Superantigens (SAgs) are highly immunostimulatory exotoxins produced by several microorganisms, mainly the gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes (34, 43). The pathophysiology associated with SAgs is linked to their ability to bypass conventional antigen peptide presentation by binding to major histocompatibility complex class II molecules on antigen-presenting cells without being internally processed and then interacting with particular external Vβ domains in the T-cell Receptors of reactive T lymphocytes, thus stimulating T-cell proliferation without regard for the antigen specificity of these cells (25, 32). The massive T-cell activation induced triggers the systemic release of proinflammatory cytokines, which has been associated with the development of toxic shock syndrome. Common toxic shock syndrome symptoms are fever, rash, hypotension, and multiple organ system dysfunction, which can eventually lead to death (4, 34). Administration of the SAg staphylococcal enterotoxin B (SEB) to BALB/c mice has been a useful model for studying some in vivo effects of superantigens. While the excessive Gamma Interferon (IFN-γ) release induced by SEB has been associated with the development of a life-threatening systemic inflammation (17) and the prevention of a protective humoral response (5), the following inhibition of IFN-γ production (15, 39) might favor bacterial dissemination and susceptibility to reinfections. We therefore believe that the study of the physiological consequences of SEB on the modulation of the IFN-γ response in vivo will be rewarding in unraveling some aspects of SAg-induced lethality and immunosuppression. An accurate regulation of the IFN-γ response from the host is required for the orchestration of effective Th1 and macrophage-rich inflammatory reactions against microbial infections (8). IFN-γ produced by T and natural killer (NK) cells interacts with a specific cell surface Receptor (IFN-γR) which is expressed on all nucleated cells at modest levels (8). IFN-γR is a heterodimeric Receptor composed of two subunits, namely, the α chain, which exhibits high-affinity ligand binding properties, and the β chain (accessory factor), which is required primarily for signaling (8). Binding to the Receptor activates signaling through the JAK/STAT pathway, which leads to STAT1α phosphorylation, dimerization, and translocation to the nucleus, where it binds to the Gamma activation site (GAS) elements in the promoters of IFN-γ-inducible genes and modulates transcription (8). IFN-γ signaling can be inhibited by other cytokines, such as interleukin-6 (IL-6) or IL-10, through STAT3-mediated activation (11, 12). IL-6 and IL-10 have been found to be able to inhibit Th1 differentiation and terminate inflammatory responses (12, 44). IL-10 can even further promote the differentiation and function of T regulatory (Treg) cells to suppress inflammatory responses or induce tolerance (15, 37, 39). The hyperresponse and the immunosuppression that follows upon SEB exposure have been studied extensively. However, these studies focused on the cellular level and on cytokine secretion but not on the modulation of the intracellular response. To gain a better understanding of the mechanism by which SAgs condition the immune responsiveness state of the host, we examined the modulation of IFN-γ production and its intracellular signaling in the in vivo response to SEB. Here we show that mouse acquisition of susceptibility to a lethal shock upon rechallenge with SEB correlates with the development of the T-cell clonal expansion phase and is associated with excessive IFN-γ production. In contrast, the IFN-γ/STAT1 signaling pathway, but not the STAT3 pathway, is selectively down-regulated in splenic T cells 72 h after the first exposure to SEB. Differential modulation of the STAT1/STAT3 signaling pathways in Th1 cells may be involved in T-cell survival and in acquisition of a suppressor phenotype upon further stimulation with the superantigen.
Ken Clarke - One of the best experts on this subject based on the ideXlab platform.
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Gamma Interferon (IFN-γ) Receptor null-mutant mice are more susceptible to herpes simplex virus type 1 infection than IFN-γ ligand null-mutant mice
Journal of virology, 1999Co-Authors: Edouard M. Cantin, Becky Tanamachi, Harry Openshaw, Jeffrey R. Mann, Ken ClarkeAbstract:Mouse strains with null mutations in the Gamma Interferon gene (Ifng) or the Gamma Interferon Receptor gene (Ifngr) have been engineered. The use of these strains as animal models of viral and bacterial infections has enhanced our understanding of the role of Gamma Interferon (IFN-γ) in the host immune response. However, direct comparisons between Ifng−/− (GKO) and Ifngr−/− (RGKO) mice have been problematic because previously available strains of these mice have had different genetic backgrounds (i.e., C57BL/6 and BALB/c for GKO mice and 129/Sv//Ev for RGKO mice). To enable direct comparison of herpes simplex virus type 1 (HSV-1) infections in GKO and RGKO mice, we introduced the IFN-γ null mutation into the 129/Sv//Ev background. We report that, after HSV-1 inoculation, mortality was significantly greater in RGKO mice than in GKO mice (38 versus 23%, P = 0.0001). Similarly, the mortality from vaccinia virus challenge was significantly greater in RGKO mice than in GKO mice. With differences in genetic background excluded as a confounding issue, these results are consistent with the existence of an alternative ligand(s) for the IFN-γ Receptor that is also capable of mediating protection against viral challenge.
