title: Characterization of a model of lethal dengue virus 2 infection in C57BL/6 mice deficient in the alpha/beta interferon receptor.
abstract: Dengue virus (DENV) causes dengue fever and dengue haemorrhagic fever/dengue shock syndrome, both considered major public-health problems worldwide. We generated a lethal DENV-2 strain (D220) by 10 additional cycles of subcutaneous inoculation of mice with supernatant from mosquito cells infected with the previously characterized strain D2S10, followed by harvesting of serum. D220 induces mortality at ten-fold lower doses than D2S10 in mice lacking only the alpha/beta interferon (IFN-α/β) receptor in C57BL/6 or 129 backgrounds under both non-enhanced and antibody-enhanced conditions. Sequence analysis of the complete viral genome revealed five amino acid changes between D220 and D2S10, of which two (K122I in envelope and V115A in NS4B) appear to account for the observed phenotypic differences between the viruses. By causing mortality at lower doses in C57BL/6 mice lacking only the IFN-α/β receptor, D220 constitutes an improved tool for study of DENV-induced pathogenesis, as well as for testing potential vaccines and antiviral drugs against DENV.
authors: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors: Susana
authors: S
authors: Orozco
authors: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors: Michael A
authors: MA
authors: Schmid
authors: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors: Poornima
authors: P
authors: Parameswaran
authors: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors: Ruben
authors: R
authors: Lachica
authors: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors: Matthew R
authors: MR
authors: Henn
authors: Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA, USA.|Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors: Robert
authors: R
authors: Beatty
authors: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors: Eva
authors: E
authors: Harris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003716:Dengue Virus / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016679:Genome, Viral; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency* / Q000235:genetics; D020539:Sequence Analysis, Protein; D019595:Severe Dengue / Q000235:genetics / Q000378:metabolism* / Q000821:virology
chemical_list: D053633:Receptor, Interferon alpha-beta