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Humanized Mice for HIV Research pp 469–479Cite as

Dengue Viral Pathogenesis and Immune Responses in Humanized Mice

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Abstract

Dengue is an insect-borne viral infection of significant global public health concern. Viral and host factors and prior humoral and cellular immunity are key contributors to severe dengue illness, dengue hemorrhagic fever (DHF). Progress in dengue research has been hampered by the lack of an ideal animal model that recapitulates key aspects of the immune responses and disease. In this regard, the generation of novel humanized mouse models presents a unique opportunity to overcome deficiencies of traditional mouse and nonhuman primate models. Two leading models of immunodeficient humanized mice, the human hematopoietic stem cell (hu-HSC) and bone marrow-liver-thymus (BLT) mice have recently been used to study dengue. Both models permit productive dengue viral infection, fever, and thrombocytopenia. Insect viral transmission has been examined in the hu-HSC model. Consistent virus-specific immunoglobulin M (IgM) responses, weak immunoglobulin G (IgG) responses with neutralizing activity, and virus-specific T cell responses are generated in hu-HSC and BLT mice. However, both humoral and cellular responses in humanized models need further improvement to match responses detected in humans. These studies are a good foundation to further our understanding of key aspects of dengue virus infection, immunity, and pathogenesis.

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Author information

Authors and Affiliations

  1. Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 01655, Worcester, MA, USA

    Anuja Mathew

  2. Department of Microbiology, Immunology and Pathology, Colorado State University, 1619 Campus delivery, 80523, Fort Collins, CO, USA

    Ramesh Akkina

Authors
  1. Anuja Mathew
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  2. Ramesh Akkina
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Corresponding authors

Correspondence to Anuja Mathew or Ramesh Akkina .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Larisa Y. Poluektova

  2. Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    J. Victor Garcia

  3. Research Center for AIDS Laboratory of Viral Pathogenesis, Kyoto University Institute for Virus Research, Sakyo-ku, Japan

    Yoshio Koyanagi

  4. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    Markus G. Manz

  5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Andrew M. Tager

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Mathew, A., Akkina, R. (2014). Dengue Viral Pathogenesis and Immune Responses in Humanized Mice. In: Poluektova, L., Garcia, J., Koyanagi, Y., Manz, M., Tager, A. (eds) Humanized Mice for HIV Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1655-9_37

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