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
Autor(es): Gardner Christina L, Burke Crystal W, Higgs Stephen T, Klimstra William B, Ryman Kate D
Resumo: In humans, chikungunya virus (CHIKV) infection causes fever, rash, - acute - 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 - caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated - contralateral limbs - dramatic inflammatory lesions, while CHIKV-181/25 vaccine - another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR - 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.
Palavras-Chave: Chikungunya; Alphavirus; Attenuation; STAT1; Polyarthralgia; Interferon; Heparan sulfate; Swelling
Imprenta: Virology, v. 425, n. 2, p. 103-112, 2012
Identificador do objeto digital: 10.1016/j.virol.2011.12.020
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology
Data de publicação: 2012
