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Flavivirus

  • Open Access
    Rapid Evolution of Enhanced Zika Virus Virulence during Direct Vertebrate Transmission Chains
    Genetic Diversity and Evolution | Spotlight
    Rapid Evolution of Enhanced Zika Virus Virulence during Direct Vertebrate Transmission Chains

    We used experimental evolution to model chains of direct and indirect Zika virus (ZIKV) transmission by serially passaging a synthetic swarm of molecularly barcoded ZIKV within and between mosquitoes and mice. We observed that direct mouse transmission chains facilitated a rapid increase in ZIKV replication and enhanced virulence in mice.

    Kasen K. Riemersma, Anna S. Jaeger, Chelsea M. Crooks, Katarina M. Braun, James Weger-Lucarelli, Gregory D. Ebel, Thomas C. Friedrich, Matthew T. Aliota
  • Substantial Attenuation of Virulence of Tembusu Virus Strain PS Is Determined by an Arginine at Residue 304 of the Envelope Protein
    Pathogenesis and Immunity
    Substantial Attenuation of Virulence of Tembusu Virus Strain PS Is Determined by an Arginine at Residue 304 of the Envelope Protein

    TMUV-related disease emerged in 2010 and has a significant economic impact on the duck industry. Although the disease was originally recognized to affect adult ducks, increasing evidence has shown that TMUV also causes severe disease of young ducklings.

    Lixin Yang, Te Liang, Junfeng Lv, Shenghua Qu, Runze Meng, Baolin Yang, Chonglun Feng, Weiqian Dai, Xiaoyan Wang, Bing Zhang, Dabing Zhang
  • Open Access
    Genome Number and Size Polymorphism in Zika Virus Infectious Units
    Genetic Diversity and Evolution
    Genome Number and Size Polymorphism in Zika Virus Infectious Units

    The arthropod-borne Zika virus (ZIKV) infects humans and can cause severe neurological sequelae, particularly in fetuses infected in utero. How this virus has been able to spread across vast geological ranges and evolve in new host populations is not yet understood.

    Nicole R. Sexton, Eric D. Bellis, Reyes A. Murrieta, Mark Cole Spangler, Parker J. Cline, James Weger-Lucarelli, Gregory D. Ebel
  • Open Access
    Two Sides of a Coin: a Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors
    Genetic Diversity and Evolution | Spotlight
    Two Sides of a Coin: a Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors

    Although Zika virus infection of pregnant women can result in congenital Zika syndrome, the factors that cause the syndrome in some but not all infected mothers are still unclear. We identified a mutation that was present in some ZIKV genomes in experimentally inoculated pregnant rhesus macaques and their fetuses. Although we did not find an association between the presence of the mutation and fetal death, we performed additional...

    Danilo Lemos, Jackson B. Stuart, William Louie, Anil Singapuri, Ana L. Ramírez, Jennifer Watanabe, Jodie Usachenko, Rebekah I. Keesler, Claudia Sanchez-San Martin, Tony Li, Calla Martyn, Glenn Oliveira, Sharada Saraf, Nathan D. Grubaugh, Kristian G. Andersen, James Thissen, Jonathan Allen, Monica Borucki, Konstantin A. Tsetsarkin, Alexander G. Pletnev, Charles Y. Chiu, Koen K. A. Van Rompay, Lark L. Coffey
  • Retinoic Acid Inducible Gene I and Protein Kinase R, but Not Stress Granules, Mediate the Proinflammatory Response to Yellow Fever Virus
    Virus-Cell Interactions
    Retinoic Acid Inducible Gene I and Protein Kinase R, but Not Stress Granules, Mediate the Proinflammatory Response to Yellow Fever Virus

    Yellow fever is a mosquito-borne acute hemorrhagic disease caused by yellow fever virus (YFV). The mechanisms responsible for its pathogenesis remain largely unknown, although increased inflammation has been linked to worsened outcome. YFV targets the liver, where it primarily infects hepatocytes. We found that two RNA-sensing proteins, RIG-I and PKR, participate in the induction of proinflammatory mediators in human hepatocytes...

    Guillaume Beauclair, Felix Streicher, Maxime Chazal, Daniela Bruni, Sarah Lesage, Ségolène Gracias, Salomé Bourgeau, Laura Sinigaglia, Takashi Fujita, Eliane F. Meurs, Frédéric Tangy, Nolwenn Jouvenet
  • Two Genetic Differences between Closely Related Zika Virus Strains Determine Pathogenic Outcome in Mice
    Pathogenesis and Immunity
    Two Genetic Differences between Closely Related Zika Virus Strains Determine Pathogenic Outcome in Mice

    Contemporary ZIKV strains are closely related and often used interchangeably in laboratory research. Here, we identify two strain-specific determinants of ZIKV virulence that are evident in only Ifnar1−/− mice but not Ifnar1−/−Ifngr1−/− DKO mice. These results identify a balanced polymorphism in the E protein that is sufficient to attenuate the PRVABC59 strain but not H/PF/...

    Derek L. Carbaugh, Shuntai Zhou, Wes Sanders, Nathaniel J. Moorman, Ronald Swanstrom, Helen M. Lazear
  • A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes
    Virus-Cell Interactions
    A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes

    Kunjin and West Nile viruses belong to the arthropod-borne flaviviruses, which can result in severe symptoms, including encephalitis, meningitis, and death. Flaviviruses have expanded into new populations and emerged as novel pathogens repeatedly in recent years, demonstrating that they remain a global threat. Currently, there are no approved antiviral therapeutics against either Kunjin or West Nile viruses. Thus, there is a pressing...

    Kelly E. Du Pont, Nicole R. Sexton, Martin McCullagh, Gregory D. Ebel, Brian J. Geiss
  • Zika Virus Subgenomic Flavivirus RNA Generation Requires Cooperativity between Duplicated RNA Structures That Are Essential for Productive Infection in Human Cells
    Genome Replication and Regulation of Viral Gene Expression | Spotlight
    Zika Virus Subgenomic Flavivirus RNA Generation Requires Cooperativity between Duplicated RNA Structures That Are Essential for Productive Infection in Human Cells

    Flaviviruses are important emerging and reemerging human pathogens. Understanding the molecular mechanisms for viral replication and evasion of host antiviral responses is relevant to development of control strategies. Flavivirus infections produce viral noncoding RNAs, known as sfRNAs, involved in viral replication and pathogenesis. In this study, we dissected molecular determinants for Zika virus sfRNA generation in the two natural...

    Horacio M. Pallarés, Guadalupe Soledad Costa Navarro, Sergio M. Villordo, Fernando Merwaiss, Luana de Borba, Maria M. Gonzalez Lopez Ledesma, Diego S. Ojeda, Annabelle Henrion-Lacritick, Maria A. Morales, Cintia Fabri, María Carla Saleh, Andrea V. Gamarnik
  • First Isolation of a Novel Aquatic Flavivirus from Chinook Salmon (<span class="named-content genus-species" id="named-content-1">Oncorhynchus tshawytscha</span>) and Its <em>In Vivo</em> Replication in a Piscine Animal Model
    Genetic Diversity and Evolution | Spotlight
    First Isolation of a Novel Aquatic Flavivirus from Chinook Salmon (Oncorhynchus tshawytscha) and Its In Vivo Replication in a Piscine Animal Model

    Chinook salmon are a keystone fish species of great ecological and commercial significance in their native northern Pacific range and in regions to which they have been introduced. Threats to salmon populations include habitat degradation, climate change, and infectious agents, including viruses. While the first isolation of a flavivirus from wild migrating salmon may indicate an emerging disease threat, characterization of the genome...

    Esteban Soto, Alvin Camus, Susan Yun, Tomofumi Kurobe, John H. Leary, Thomas G. Rosser, Jennifer A. Dill-Okubo, Akinyi Carol Nyaoke, Mark Adkison, Allan Renger, Terry Fei Fan Ng
  • Open Access
    A Molecular Determinant of West Nile Virus Secretion and Morphology as a Target for Viral Attenuation
    Virus-Cell Interactions
    A Molecular Determinant of West Nile Virus Secretion and Morphology as a Target for Viral Attenuation

    West Nile virus (WNV) is a worldwide (re)emerging mosquito-transmitted Flavivirus causing fatal neurological diseases in humans. However, no human vaccine has been yet approved. One of the most effective live-attenuated vaccines was empirically obtained by serial passaging of wild-type yellow fever Flavivirus. However, such an approach is not acceptable nowadays, and the development of a rationally designed vaccine is...

    Justine Basset, Julien Burlaud-Gaillard, Maxence Feher, Philippe Roingeard, Félix A. Rey, Nathalie Pardigon

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