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pathogenesis

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    Middle East Respiratory Syndrome Coronavirus Gene 5 Modulates Pathogenesis in Mice
    Pathogenesis and Immunity
    Middle East Respiratory Syndrome Coronavirus Gene 5 Modulates Pathogenesis in Mice

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus causing human infections with high mortality rate (∼35%). Animal models together with reverse-genetics systems are essential to understand MERS-CoV pathogenesis. We developed a reverse-genetics system for a mouse-adapted MERS-CoV that reproduces the virus behavior observed in humans. This system is highly useful to investigate the role of specific viral genes in...

    Javier Gutierrez-Alvarez, Li Wang, Raul Fernandez-Delgado, Kun Li, Paul B. McCray, Stanley Perlman, Isabel Sola, Sonia Zuñiga, Luis Enjuanes
  • Marek’s Disease Virus Requires Both Copies of the Inverted Repeat Regions for Efficient <em>In Vivo</em> Replication and Pathogenesis
    Pathogenesis and Immunity
    Marek’s Disease Virus Requires Both Copies of the Inverted Repeat Regions for Efficient In Vivo Replication and Pathogenesis

    Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes losses in the poultry industry of up to $2 billion per year. The virus is also widely used as a model to study alphaherpesvirus pathogenesis and virus-induced tumor development in a natural host. MDV and most other herpesviruses harbor direct or inverted repeats regions in their genome. However, the role of these sequence duplications in...

    Tereza Vychodil, Andelé M. Conradie, Jakob Trimpert, Amr Aswad, Luca D. Bertzbach, Benedikt B. Kaufer
  • Open Access
    Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues
    Pathogenesis and Immunity
    Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues

    Lassa fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa fever outbreak in Nigeria indicating that severe Lassa fever is associated with activation of T cells antigenically unrelated to...

    Julia R. Port, David M. Wozniak, Lisa Oestereich, Elisa Pallasch, Beate Becker-Ziaja, Jonas Müller, Monika Rottstegge, Catherine Olal, Sergio Gómez-Medina, Jennifer Oyakhliome, Yemisi Ighodalo, Emmanuel Omomoh, Thomas Olokor, Donatus I. Adomeh, Danny Asogun, Ephraim Ogbani-Emovon, Kristin Hartmann, Susanne Krasemann, Emily V. Nelson, Beatriz Escudero-Pérez, Anita K. McElroy, Stephan Günther, César Muñoz-Fontela
  • Inactivating Three Interferon Antagonists Attenuates Pathogenesis of an Enteric Coronavirus
    Pathogenesis and Immunity
    Inactivating Three Interferon Antagonists Attenuates Pathogenesis of an Enteric Coronavirus

    Emerging coronaviruses, including SARS-CoV-2 and porcine CoVs, can infect enterocytes, cause diarrhea, and be shed in the feces. New approaches are needed to understand enteric pathogenesis and to develop vaccines and therapeutics to prevent the spread of these viruses. Here, we exploited a reverse genetic system for an enteric CoV, porcine epidemic diarrhea virus (PEDV), and outline an approach of genetically inactivating highly...

    Xufang Deng, Alexandra C. Buckley, Angela Pillatzki, Kelly M. Lager, Kay S. Faaberg, Susan C. Baker
  • Early Transcriptional Changes within Liver, Adrenal Gland, and Lymphoid Tissues Significantly Contribute to Ebola Virus Pathogenesis in Cynomolgus Macaques
    Pathogenesis and Immunity
    Early Transcriptional Changes within Liver, Adrenal Gland, and Lymphoid Tissues Significantly Contribute to Ebola Virus Pathogenesis in Cynomolgus Macaques

    Ebola virus (EBOV) remains a high-priority pathogen since it continues to cause outbreaks with high case fatality rates. Although it is well established that EBOV results in severe organ damage, our understanding of tissue injury in the liver, adrenal glands, and lymphoid tissues remains limited. We begin to address this knowledge gap by conducting longitudinal gene expression studies in these tissues, which were collected from EBOV-...

    Allen Jankeel, Andrea R. Menicucci, Courtney Woolsey, Karla A. Fenton, Norma Mendoza, Krista Versteeg, Robert W. Cross, Thomas W. Geisbert, Ilhem Messaoudi
  • Gp37 Regulates the Pathogenesis of Avian Leukosis Virus Subgroup J via Its C Terminus
    Pathogenesis and Immunity
    Gp37 Regulates the Pathogenesis of Avian Leukosis Virus Subgroup J via Its C Terminus

    ALV-J can cause severe immunosuppression and myeloid leukemia in infected chickens. However, no vaccine or antiviral drug is available against ALV-J, and the mechanism for ALV-J pathogenesis needs to be elucidated. It is generally believed that gp85 and LTR of ALV contribute to its pathogenesis. Here, we found that the C terminus and the tyrosine motifs (YxxM, ITIM, and ITAM-like) in the CTD of Gp37 of ALV-J could...

    Tuofan Li, Xiaohui Yao, Chunping Li, Jun Zhang, Quan Xie, Weikang Wang, Hao Lu, Hui Fu, Luyuan Li, Jing Xie, Hongxia Shao, Wei Gao, Aijian Qin, Jianqiang Ye
  • Open Access
    Ovine Herpesvirus 2 Encodes a Previously Unrecognized Protein, pOv8.25, That Targets Mitochondria and Triggers Apoptotic Cell Death
    Virus-Cell Interactions
    Ovine Herpesvirus 2 Encodes a Previously Unrecognized Protein, pOv8.25, That Targets Mitochondria and Triggers Apoptotic Cell Death

    Ovine herpesvirus 2 (OvHV-2) circulates among sheep without causing disease. However, upon transmission to cattle, the same virus instigates a frequently lethal disease, malignant catarrhal fever (MCF). While the cause of death and pathogenesis of tissue lesions are still poorly understood, MCF is characterized by the accumulation of lymphocytes in various tissues, associated with vasculitis and cell death. As infectious virus is hardly...

    Neeta Shrestha, Kurt Tobler, Stephanie Uster, Romina Sigrist-Nagy, Melanie Michaela Hierweger, Mathias Ackermann
  • An Animal Model That Mimics Human Herpesvirus 6B Pathogenesis
    Pathogenesis and Immunity
    An Animal Model That Mimics Human Herpesvirus 6B Pathogenesis

    Human herpesvirus 6B (HHV-6B) is a ubiquitous virus that establishes lifelong latent infection only in humans, and the infection can reactivate, with severe complications that cause major problems. A small-animal model of HHV-6B infection has thus been desired for research regarding the pathogenicity of HHV-6B and the development of antiviral agents. We generated humanized mice by transplantation with human hematopoietic stem cells, and...

    Bochao Wang, Yasuyuki Saito, Mitsuhiro Nishimura, Zhenxiao Ren, Lidya Handayani Tjan, Alaa Refaat, Rie Iida-Norita, Ryuko Tsukamoto, Masato Komatsu, Tomoo Itoh, Takashi Matozaki, Yasuko Mori
  • Hemagglutinin Stability Regulates H1N1 Influenza Virus Replication and Pathogenicity in Mice by Modulating Type I Interferon Responses in Dendritic Cells
    Pathogenesis and Immunity | Spotlight
    Hemagglutinin Stability Regulates H1N1 Influenza Virus Replication and Pathogenicity in Mice by Modulating Type I Interferon Responses in Dendritic Cells

    Diverse influenza A viruses circulate in wild aquatic birds, occasionally infecting farm animals. Rarely, an avian- or swine-origin influenza virus adapts to humans and starts a pandemic. Seasonal and many universal influenza vaccines target the HA surface protein, which is a key component of pandemic influenza viruses. Understanding the HA properties needed for replication and pathogenicity in mammals may guide response efforts to...

    Marion Russier, Guohua Yang, Benoit Briard, Victoria Meliopoulos, Sean Cherry, Thirumala-Devi Kanneganti, Stacey Schultz-Cherry, Peter Vogel, Charles J. Russell
  • What a Difference a Gene Makes: Identification of Virulence Factors of Cowpox Virus
    Pathogenesis and Immunity
    What a Difference a Gene Makes: Identification of Virulence Factors of Cowpox Virus

    With the cessation of vaccination against smallpox and its assumed cross-protectivity against other OPV infections, waning immunity could open up new niches for related poxviruses. Therefore, the identification of virulence mechanisms in CPXV is of general interest. Here, we aimed to identify virulence markers in an experimental rodent CPXV infection model using bacterial artificial chromosome (BAC)-based virus recombineering. We...

    Aistė Tamošiūnaitė, Saskia Weber, Timo Schippers, Annika Franke, Zhiyong Xu, Maria Jenckel, Florian Pfaff, Donata Hoffmann, Maegan Newell, B. Karsten Tischer, Martin Beer, Nikolaus Osterrieder

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