title: Animal models of dengue virus infection.
abstract: The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the 'vascular-leak' syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720, USA. simona.zompi@gmail.com
authors.forename: Simona
authors.initials: S
authors.lastname: Zompi
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002678:Chimera; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003715:Dengue / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology / Q000635:transmission; D053059:Dengue Vaccines; D003716:Dengue Virus / Q000472:pathogenicity / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D018380:Hematopoietic Stem Cell Transplantation; D058507:Host Specificity; D006801:Humans; D007111:Immunity, Cellular; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D008253:Macaca mulatta; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D014766:Viremia / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D053059:Dengue Vaccines; C508032:Ifnar1 protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse; D050795:STAT2 Transcription Factor; C494085:Stat2 protein, mouse; D053633:Receptor, Interferon alpha-beta