Journal
VIROLOGY
Volume 425, Issue 2, Pages 103-112Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.12.020
Keywords
Chikungunya; Alphavirus; Attenuation; STAT1; Polyarthralgia; Interferon; Heparan sulfate; Swelling
Categories
Funding
- National Institute of Allergy and Infectious Diseases (NIAID) [R21 AI076894-01, R21 AI072350-01, R01 AI083383]
- NIAID through the Pacific Northwest (PNWRCE) [U54 AI081680]
- NIAID through Western (WRCE) [U54 AI057156-061]
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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. (C) 2012 Elsevier Inc. All rights reserved.
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