The Experts below are selected from a list of 3489 Experts worldwide ranked by ideXlab platform

Eric Bergeron - One of the best experts on this subject based on the ideXlab platform.

Stuart T. Nichol - One of the best experts on this subject based on the ideXlab platform.

  • heterologous protection against crimean congo Hemorrhagic Fever in mice after a single dose of replicon particle vaccine
    Antiviral Research, 2019
    Co-Authors: Jessica R Spengler, Eric Bergeron, Stuart T. Nichol, Florine E M Scholte, Stephen R Welch, Jessica R. Harmon, Joann D Colemanmccray, Christina F. Spiropoulou
    Abstract:

    No vaccines are currently licensed to prevent Crimean-Congo Hemorrhagic Fever virus (CCHFV) infection, which can cause mild self-limiting clinical signs or severe, often fatal Hemorrhagic Fever disease. Here we continued investigations into the utility of a single-dose virus replicon particle (VRP) vaccine regimen by assessing protection against Turkey or Oman strains of CCHFV. We found that all mice were completely protected from disease, supporting broad applicability of this platform for CCHFV prevention.

  • stable occupancy of the crimean congo Hemorrhagic Fever virus encoded deubiquitinase blocks viral infection
    Mbio, 2019
    Co-Authors: Florine E M Scholte, J.v. Dzimianski, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Joann D Colemanmccray, Brian L Hua, Laura K Mcmullan, Christina F. Spiropoulou
    Abstract:

    ABSTRACT Crimean-Congo Hemorrhagic Fever virus (CCHFV) infection can result in a severe Hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU’s immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs. IMPORTANCE Crimean-Congo Hemorrhagic Fever virus is an important human pathogen with a wide global distribution for which no therapeutic interventions are available. CCHFV encodes a cysteine protease belonging to the ovarian tumor (OTU) family which is involved in host immune suppression. Here we demonstrate that artificially prolonged binding of the OTU to a substrate inhibits virus infection. This provides novel insights into CCHFV OTU function during the viral replicative cycle and highlights the OTU as a potential antiviral target.

  • single dose replicon particle vaccine provides complete protection against crimean congo Hemorrhagic Fever virus in mice
    Emerging microbes & infections, 2019
    Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Brendan T. Freitas, Markus H. Kainulainen, Joann D Colemanmccray, Eric Bergeron
    Abstract:

    Crimean-Congo Hemorrhagic Fever virus (CCHFV) is an emerging tick-borne virus from the family Nairoviridae that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution,...

  • Single-dose replicon particle vaccine provides complete protection against Crimean-Congo Hemorrhagic Fever virus in mice
    2019
    Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Joann D. Coleman-mccray, Brendan T. Freitas, Markus H. Kainulainen, Eric Bergeron
    Abstract:

    Single-dose replicon particle vaccine provides complete protection against Crimean-Congo Hemorrhagic Fever virus in mic

  • crimean congo Hemorrhagic Fever virus suppresses innate immune responses via a ubiquitin and isg15 specific protease
    Cell Reports, 2017
    Co-Authors: Florine E M Scholte, J.v. Dzimianski, Christina F. Spiropoulou, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Marko Zivcec, Michelle K Deaton, Stephen R Welch, Eric Bergeron
    Abstract:

    Antiviral responses are regulated by conjugation of ubiquitin (Ub) and interferon-stimulated gene 15 (ISG15) to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU) superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo Hemorrhagic Fever virus (CCHFV, family Nairoviridae) is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase. We investigated CCHFV OTU function by inactivating protease catalytic activity or by selectively disrupting its deubiquitinase and deISGylase activity using reverse genetics. CCHFV OTU inactivation blocked viral replication independently of its RNA polymerase activity, while deubiquitinase activity proved critical for suppressing the interferon responses. Our findings provide insights into viral OTU functions and support the development of therapeutics and vaccines.

Ali Mirazimi - One of the best experts on this subject based on the ideXlab platform.

  • The DEVD motif of Crimean-Congo Hemorrhagic Fever virus nucleoprotein is essential for viral replication in tick cells
    2019
    Co-Authors: Cristiano Salata, Eric Bergeron, Stéphanie Devignot, Friedemann Weber, Lesley Bell-sakyi, Vanessa Monteil, Helen Karlberg, Michele Celestino, Mikael Leijon, Ali Mirazimi
    Abstract:

    The DEVD motif of Crimean-Congo Hemorrhagic Fever virus nucleoprotein is essential for viral replication in tick cell

  • structure of crimean congo Hemorrhagic Fever virus nucleoprotein superhelical homo oligomers and the role of caspase 3 cleavage
    Journal of Virology, 2012
    Co-Authors: Yi Wang, Stéphanie Devignot, Friedemann Weber, Helen Karlberg, Sujit Dutta, Quan Hao, Yeejoo Tan, Ali Mirazimi
    Abstract:

    Crimean-Congo Hemorrhagic Fever, a severe Hemorrhagic disease found throughout Africa, Europe, and Asia, is caused by the tick-borne Crimean-Congo Hemorrhagic Fever virus (CCHFV). CCHFV is a negative-sense single-stranded RNA (ssRNA) virus belonging to the Nairovirus genus of the Bunyaviridae family. Its genome of three single-stranded RNA segments is encapsidated by the nucleocapsid protein (CCHFV N) to form the ribonucleoprotein complex. This ribonucleoprotein complex is required during replication and transcription of the viral genomic RNA. Here, we present the crystal structures of the CCHFV N in two distinct forms, an oligomeric form comprised of double antiparallel superhelices and a monomeric form. The head-to-tail interaction of the stalk region of one CCHFV N subunit with the base of the globular body of the adjacent subunit stabilizes the helical organization of the oligomeric form of CCHFV N. It also masks the conserved caspase-3 cleavage site present at the tip of the stalk region from host cell caspase-3 interaction and cleavage. By incubation with primer-length ssRNAs, we also obtained the crystal structure of CCHFV N in its monomeric form, which is similar to a recently published structure. The conformational change of CCHFV N upon deoligomerization results in the exposure of the caspase-3 cleavage site and subjects CCHFV N to caspase-3 cleavage. Mutations of this cleavage site inhibit cleavage by caspase-3 and result in enhanced viral polymerase activity. Thus, cleavage of CCHFV N by host cell caspase-3 appears to be crucial for controlling viral RNA synthesis and represents an important host defense mechanism against CCHFV infection.

  • healthy individuals immune response to the bulgarian crimean congo Hemorrhagic Fever virus vaccine
    Vaccine, 2012
    Co-Authors: Mehrdad Mousavijazi, Anna Papa, Iva Christova, Helen Karlberg, Ali Mirazimi
    Abstract:

    Crimean-Congo Hemorrhagic Fever virus (CCHFV) poses a great threat to public health due to its high mortality and transmission rate and wide geographical distribution. There is currently no specific antiviral therapy for CCHF. This study provides the first in-depth analysis of the cellular and humoral immune response in healthy individuals following injection of inactivated Bulgarian vaccine, the only CCHFV vaccine available at present. Vaccinated individuals developed robust, anti-CCHFV-specific T-cell activity as measured by IFN-γ ELISpot assay. The frequency of IFN-γ secreting T-cells was 10-fold higher in individuals after vaccination with four doses than after one single dose. High levels of CCHFV antibodies were observed following the first dose, but repeated doses were required to achieve antibodies with neutralizing activity against CCHFV. However, the neutralizing activity in these groups was low.

  • crimean congo Hemorrhagic Fever virus infection is lethal for adult type i interferon receptor knockout mice
    Journal of General Virology, 2010
    Co-Authors: Sandor Bereczky, Helen Karlberg, Gunnel Lindegren, Sara Akerstrom, Jonas Klingstrom, Ali Mirazimi
    Abstract:

    Crimean–Congo Hemorrhagic Fever virus (CCHFV) poses a great threat to public health due to its high mortality, transmission and geographical distribution. To date, there is no vaccine or specific treatment available and the knowledge regarding its pathogenesis is highly limited. Using a small-animal model system, this study showed that adult mice missing the type I interferon (IFN) receptor (IFNAR−/−) were susceptible to CCHFV and developed an acute disease with fatal outcome. In contrast, infection of wild-type mice (129 Sv/Ew) was asymptomatic. Viral RNA was found in all analysed organs of the infected mice, but the amount of CCHFV RNA was significantly higher in the IFNAR−/− mice than in the wild-type mice. Furthermore, the liver of IFNAR−/− mice was enlarged significantly, showing that IFN is important for limiting virus spread and protecting against liver damage in mice.

  • crimean congo Hemorrhagic Fever virus infects human monocyte derived dendritic cells
    Virology, 2009
    Co-Authors: Annemarie Connollyandersen, Iyadh Douagi, Annette A Kraus, Ali Mirazimi
    Abstract:

    For some patients infection with Crimean Congo Hemorrhagic Fever virus (CCHFV) causes a severe disease characterized by Fever, vascular leakage and coagulopathy. Knowledge of CCHF pathogenesis is limited and today there is no information about the specific target cells of CCHFV. In this study we analyzed the permissiveness of human peripheral blood mononuclear cells (PBMCs) including monocyte-derived dendritic cells (moDCs) to CCHFV infection. Interestingly, we found that moDCs are the most permissive to CCHFV infection and this infection induced cytokine release from moDCs. Furthermore, supernatants from infected moDCs were found to activate human endothelial cells.

Florine E M Scholte - One of the best experts on this subject based on the ideXlab platform.

  • fluorescent crimean congo Hemorrhagic Fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in ifnar mice
    PLOS Pathogens, 2019
    Co-Authors: Stephen R Welch, Eric Bergeron, Florine E M Scholte, Jessica R. Harmon, Joann D Colemanmccray, Gary P. Kobinger, Jana M Ritter, Anita K Mcelroy, Sherif R Zaki
    Abstract:

    Crimean-Congo Hemorrhagic Fever virus (CCHFV, order Bunyavirales, family Nairoviridae, genus Orthonairovirus) is the tick-borne etiological agent of Crimean-Congo Hemorrhagic Fever (CCHF) in humans. Animals are generally susceptible to CCHFV infection but refractory to disease. Small animal models are limited to interferon-deficient mice, that develop acute fatal disease following infection. Here, using a ZsGreen1- (ZsG) expressing reporter virus (CCHFV/ZsG), we examine tissue tropism and dissemination of virus in interferon-α/β receptor knock-out (Ifnar-/-) mice. We demonstrate that CCHFV/ZsG retains in vivo pathogenicity comparable to wild-type virus. Interestingly, despite high levels of viral RNA in all organs assessed, 2 distribution patterns of infection were observed by both fluorescence and immunohistochemistry (IHC), corresponding to the permissiveness of organ tissues. To further investigate viral dissemination and to temporally define cellular targets of CCHFV in vivo, mice were serially euthanized at different stages of disease. Flow cytometry was used to characterize CCHFV-associated alterations in hematopoietic cell populations and to classify infected cells in the blood, lymph node, spleen, and liver. ZsG signal indicated that mononuclear phagocytic cells in the lymphatic tissues were early targets of infection; in late-stage infection, overall, the highest levels of signal were detected in the liver, and ZsG was found in both antigen-presenting and lymphocyte cell populations.

  • heterologous protection against crimean congo Hemorrhagic Fever in mice after a single dose of replicon particle vaccine
    Antiviral Research, 2019
    Co-Authors: Jessica R Spengler, Eric Bergeron, Stuart T. Nichol, Florine E M Scholte, Stephen R Welch, Jessica R. Harmon, Joann D Colemanmccray, Christina F. Spiropoulou
    Abstract:

    No vaccines are currently licensed to prevent Crimean-Congo Hemorrhagic Fever virus (CCHFV) infection, which can cause mild self-limiting clinical signs or severe, often fatal Hemorrhagic Fever disease. Here we continued investigations into the utility of a single-dose virus replicon particle (VRP) vaccine regimen by assessing protection against Turkey or Oman strains of CCHFV. We found that all mice were completely protected from disease, supporting broad applicability of this platform for CCHFV prevention.

  • stable occupancy of the crimean congo Hemorrhagic Fever virus encoded deubiquitinase blocks viral infection
    Mbio, 2019
    Co-Authors: Florine E M Scholte, J.v. Dzimianski, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Joann D Colemanmccray, Brian L Hua, Laura K Mcmullan, Christina F. Spiropoulou
    Abstract:

    ABSTRACT Crimean-Congo Hemorrhagic Fever virus (CCHFV) infection can result in a severe Hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU’s immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs. IMPORTANCE Crimean-Congo Hemorrhagic Fever virus is an important human pathogen with a wide global distribution for which no therapeutic interventions are available. CCHFV encodes a cysteine protease belonging to the ovarian tumor (OTU) family which is involved in host immune suppression. Here we demonstrate that artificially prolonged binding of the OTU to a substrate inhibits virus infection. This provides novel insights into CCHFV OTU function during the viral replicative cycle and highlights the OTU as a potential antiviral target.

  • single dose replicon particle vaccine provides complete protection against crimean congo Hemorrhagic Fever virus in mice
    Emerging microbes & infections, 2019
    Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Brendan T. Freitas, Markus H. Kainulainen, Joann D Colemanmccray, Eric Bergeron
    Abstract:

    Crimean-Congo Hemorrhagic Fever virus (CCHFV) is an emerging tick-borne virus from the family Nairoviridae that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution,...

  • Single-dose replicon particle vaccine provides complete protection against Crimean-Congo Hemorrhagic Fever virus in mice
    2019
    Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Joann D. Coleman-mccray, Brendan T. Freitas, Markus H. Kainulainen, Eric Bergeron
    Abstract:

    Single-dose replicon particle vaccine provides complete protection against Crimean-Congo Hemorrhagic Fever virus in mic

Jessica R Spengler - One of the best experts on this subject based on the ideXlab platform.

  • heterologous protection against crimean congo Hemorrhagic Fever in mice after a single dose of replicon particle vaccine
    Antiviral Research, 2019
    Co-Authors: Jessica R Spengler, Eric Bergeron, Stuart T. Nichol, Florine E M Scholte, Stephen R Welch, Jessica R. Harmon, Joann D Colemanmccray, Christina F. Spiropoulou
    Abstract:

    No vaccines are currently licensed to prevent Crimean-Congo Hemorrhagic Fever virus (CCHFV) infection, which can cause mild self-limiting clinical signs or severe, often fatal Hemorrhagic Fever disease. Here we continued investigations into the utility of a single-dose virus replicon particle (VRP) vaccine regimen by assessing protection against Turkey or Oman strains of CCHFV. We found that all mice were completely protected from disease, supporting broad applicability of this platform for CCHFV prevention.

  • stable occupancy of the crimean congo Hemorrhagic Fever virus encoded deubiquitinase blocks viral infection
    Mbio, 2019
    Co-Authors: Florine E M Scholte, J.v. Dzimianski, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Joann D Colemanmccray, Brian L Hua, Laura K Mcmullan, Christina F. Spiropoulou
    Abstract:

    ABSTRACT Crimean-Congo Hemorrhagic Fever virus (CCHFV) infection can result in a severe Hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU’s immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs. IMPORTANCE Crimean-Congo Hemorrhagic Fever virus is an important human pathogen with a wide global distribution for which no therapeutic interventions are available. CCHFV encodes a cysteine protease belonging to the ovarian tumor (OTU) family which is involved in host immune suppression. Here we demonstrate that artificially prolonged binding of the OTU to a substrate inhibits virus infection. This provides novel insights into CCHFV OTU function during the viral replicative cycle and highlights the OTU as a potential antiviral target.

  • single dose replicon particle vaccine provides complete protection against crimean congo Hemorrhagic Fever virus in mice
    Emerging microbes & infections, 2019
    Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Brendan T. Freitas, Markus H. Kainulainen, Joann D Colemanmccray, Eric Bergeron
    Abstract:

    Crimean-Congo Hemorrhagic Fever virus (CCHFV) is an emerging tick-borne virus from the family Nairoviridae that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution,...

  • Single-dose replicon particle vaccine provides complete protection against Crimean-Congo Hemorrhagic Fever virus in mice
    2019
    Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Joann D. Coleman-mccray, Brendan T. Freitas, Markus H. Kainulainen, Eric Bergeron
    Abstract:

    Single-dose replicon particle vaccine provides complete protection against Crimean-Congo Hemorrhagic Fever virus in mic

  • crimean congo Hemorrhagic Fever virus suppresses innate immune responses via a ubiquitin and isg15 specific protease
    Cell Reports, 2017
    Co-Authors: Florine E M Scholte, J.v. Dzimianski, Christina F. Spiropoulou, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Marko Zivcec, Michelle K Deaton, Stephen R Welch, Eric Bergeron
    Abstract:

    Antiviral responses are regulated by conjugation of ubiquitin (Ub) and interferon-stimulated gene 15 (ISG15) to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU) superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo Hemorrhagic Fever virus (CCHFV, family Nairoviridae) is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase. We investigated CCHFV OTU function by inactivating protease catalytic activity or by selectively disrupting its deubiquitinase and deISGylase activity using reverse genetics. CCHFV OTU inactivation blocked viral replication independently of its RNA polymerase activity, while deubiquitinase activity proved critical for suppressing the interferon responses. Our findings provide insights into viral OTU functions and support the development of therapeutics and vaccines.