Protection against Chikungunya virus induced arthralgia following prophylactic treatment with adenovirus vectored interferon (mDEF201)
Autor(es): Dagley Ashley, Ennis Jane, Turner Jeffrey D, Rood Kerry A, Van Wettere Arnaud J, Gowen Brian B, Julander Justin G
Resumo: Recent outbreaks of Chikungunya virus (CHIKV) infection have resulted in millions of cases of disease with significant morbidity. No approved antiviral treatments exist for the prevention or treatment of this viral disease. Infection with CHIKV results in a high rate of symptomatic disease that primarily includes a debilitating arthralgia. To model this cardinal disease manifestation, adult DBA/1J mice were challenged with CHIKV by footpad injection. Viremia - hind limb virus titers increased ?100-fold while spleen virus increased >1000-fold within 1day post-virus infection (dpi). Footpad swelling was measured over a 10-day period, with peak swelling observed between 6 - 7dpi. Histology of the hind leg at the site of virus challenge showed evidence of myositis - synovitis starting on 5dpi. Cytokine profiling of the hind limb at the site of inoculation revealed a biphasic inflammatory response represented by an increase in IL-6, MCP-1, IFN-?, MIP-1?, RANTES, - IL-17. To investigate the prophylactic capacity of IFN, mice were treated with mDEF201, an adenovirus-vectored IFN-?. Intranasal administration of a single 10(7)pfu/ml dose of mDEF201 administered 21days to 24h prior to infection, significantly reduced footpad swelling, virus titers in the hind leg - spleen, - several inflammatory cytokines. Efficacy was not observed when treatment was initiated 24h after virus challenge. This arthralgia model of CHIKV recapitulates relevant disease features commonly observed in human disease making it applicable to preclinical testing of therapies that target both viral replication - the associated joint disease.
Palavras-Chave: Antiviral; Arthritis; Chikungunya; Interferon; Mouse model; mDEF201
Imprenta: Antiviral Research, v. 108, p. 1-9, 2014
Identificador do objeto digital: 10.1016/j.antiviral.2014.05.004
Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever
Data de publicação: 2014
