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.
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.
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DOI：
10.1016/j.virol.2011.12.020
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发表时间：
2012-04-10
期刊：
影响因子：
3.7
通讯作者：
Ryman KD
中科院分区：
文献类型：
--
作者：
Gardner CL;Burke CW;Higgs ST;Klimstra WB;Ryman KD
在人类中，基孔肯雅病毒（CHIKV）感染可引起发热、皮疹以及伴有关节肿胀的急性和持续性多关节痛/关节炎。我们报告了一种新的成年小鼠CHIKV疾病模型，该模型将野生型CHIKV- lr毒株与减毒活疫苗毒株（CHIKV-181/25）区分开来。虽然在后足垫接种的8周龄正常小鼠没有后肢肿胀，但CHIKV-LR在肌肉骨骼组织中复制并引起可检测的炎症。在缺乏stat1依赖性干扰素（IFN）应答的小鼠中，CHIKV-LR引起接种和对侧肢体明显肿胀和剧烈炎症病变，而CHIKV-181/25疫苗和另一种关节炎源性甲病毒Sindbis未能诱导肿胀。在体外树突状细胞中，IFN应答同样抑制CHIKV-LR和CHIKV-181/25的复制，而巨噬细胞对感染不依赖于stat1介导的IFN应答。由于CHIKV- lr的传染性不依赖于GAG，而CHIKV-181/25的传染性高度依赖于GAG，因此与糖胺聚糖（Glycosaminoglycan， GAG）结合可能是CHIKV疫苗的一种衰减机制。
In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthalgia/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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DOI：
10.1093/infdis/jiq042
发表时间：
2011-01-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Chow A;Her Z;Ong EK;Chen JM;Dimatatac F;Kwek DJ;Barkham T;Yang H;Rénia L;Leo YS;Ng LF
通讯作者：
Ng LF
影响因子：
3.7
作者：
Burke, Crystal W.;Gardner, Christina L.;Steffan, Joshua J.;Ryman, Kate D.;Klimstra, William B.
通讯作者：
Klimstra, William B.
影响因子：
5.4
作者：
Brynes, AP;Griffin, DE
通讯作者：
Griffin, DE
影响因子：
3.7
作者：
Ozden S;Huerre M;Riviere JP;Coffey LL;Afonso PV;Mouly V;de Monredon J;Roger JC;El Amrani M;Yvin JL;Jaffar MC;Frenkiel MP;Sourisseau M;Schwartz O;Butler-Browne G;Desprès P;Gessain A;Ceccaldi PE
通讯作者：
Ceccaldi PE
影响因子：
3.4
作者：
BRIGHTON, SW;SIMSON, IW
通讯作者：
SIMSON, IW