Unbound MEDLINE

Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate.

Abstract

In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthralgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent.

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  • Publisher Full Text
  • Authors

    Gardner CL, Burke CW, Higgs ST, Klimstra WB, Ryman KD

    Institution

    Center for Vaccine Research and Dept. of Microbiology & Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

    Source

    Virology 425:2 2012 Apr 10 pg 103-12

    MeSH

    Alphavirus Infections
    Animals
    Arthritis, Infectious
    Chikungunya virus
    Disease Models, Animal
    Humans
    Interferon-alpha
    Interferon-beta
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Vaccines, Attenuated
    Viral Vaccines
    Virus Replication

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22305131