| Title | 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. | | Author(s) | 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 2012 Apr 10; 425(2):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
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 22305131 |
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