Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models.
Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models.
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DOI：
10.1128/mbio.02449-17
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发表时间：
2018-03-06
期刊：
影响因子：
6.4
通讯作者：
Rossi SL
中科院分区：
文献类型：
--
作者：
Langsjoen RM;Haller SL;Roy CJ;Vinet-Oliphant H;Bergren NA;Erasmus JH;Livengood JA;Powell TD;Weaver SC;Rossi SL
基孔肯雅病毒（CHIKV）是一种重新出现的虫媒病毒，能够引起发热性疾病、多关节炎和多关节痛的爆发性爆发，给受影响人群带来严重的发病率。 CHIKV 在基因上可分为 3 个主要谱系：西非 (WA)；东非、中非和南非 (ECSA)；印度洋（IOL）；和亚洲人。此外，印度洋（IOL）亚系出现在 ECSA 分支内，亚洲/美洲亚系出现在亚洲分支内。虽然不同 CHIKV 谱系和亚谱系的暴发流行病学和病理学特征存在差异，但比较谱系毒力水平的有针对性的调查却很少报道。我们比较了 I 型干扰素受体敲除 A129 小鼠模型中代表所有主要谱系和亚谱系的 CHIKV 分离株的毒力水平，发现了谱系特异性的毒力差异。我们还在小鼠和非人灵长类动物模型中评估了 IOL 衍生减毒活疫苗株 CHIKV/IRESv1 对亚洲/美国 CHIKV 分离株 YO123223 以及小鼠模型中 WA 株 SH2830 的交叉保护功效。 CHIKV/IRES 疫苗为小鼠和非人灵长类动物群体提供了针对加勒比毒株挑战的保护，并保护小鼠免受 WA 挑战。总而言之，我们的数据表明，亚洲/美国 CHIKV 毒株的毒力低于亚洲、ECSA 和 WA 谱系的毒力，尽管毒力存在差异，但基于 IOL 的疫苗毒株可针对其他谱系的毒株提供强大的交叉保护。需要进一步的研究来阐明 A129 小鼠模型中 CHIKV 毒力变异的遗传基础，并证实这种变异与人类致病性。基孔肯雅病毒 (CHIKV) 是一种重新出现的人类病原体，能够引起使人衰弱和毁容的多关节炎，在最初的发烧消退后，这种症状可持续数月至数年。 CHIKV 有四种主要遗传谱系，以及最近出现的两个亚谱系，但尚未评估其中任何一个亚谱系的毒力差异。此外，基孔肯雅疫苗针对异源 CHIKV 谱系的交叉保护能力尚未得到探索。因此，我们试图比较 CHIKV 谱系之间的毒力水平，并评估 CHIKV/IRESv1 候选疫苗在两种不同的 CHIKV 感染模型中的交叉保护功效。我们的结果表明，尽管在 CHIKV 谱系之间观察到毒力存在显着差异，但 CHIKV/IRESv1 疫苗可引发跨谱系保护性免疫。这些发现为预测未来疫情中 CHIKV 相关发病的严重程度以及疫苗开发考虑因素提供了有价值的信息。
Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported. We compared the virulence levels of CHIKV isolates representing all major lineages and sublineages in the type I interferon receptor-knockout A129 mouse model and found lineage-specific differences in virulence. We also evaluated the cross-protective efficacy of the IOL-derived, live-attenuated vaccine strain CHIKV/IRESv1 against the Asian/American CHIKV isolate YO123223 in both murine and nonhuman primate models, as well as the WA strain SH2830 in a murine model. The CHIKV/IRES vaccine provided protection both in mice and in nonhuman primate cohorts against Caribbean strain challenge and protected mice against WA challenge. Taken together, our data suggest that Asian/American CHIKV strains are less virulent than those in the Asian, ECSA, and WA lineages and that despite differences in virulence, IOL-based vaccine strains offer robust cross-protection against strains from other lineages. Further research is needed to elucidate the genetic basis for variation in CHIKV virulence in the A129 mouse model and to corroborate this variation with human pathogenicity. Chikungunya virus (CHIKV) is a reemerging human pathogen capable of causing debilitating and disfiguring polyarthritis, which can last for months to years after initial fever has resolved. There are four major genetic lineages of CHIKV, as well as two recently emerged sublineages, none of which have been evaluated for differences in virulence. Moreover, the ability of chikungunya vaccines to cross-protect against heterologous CHIKV lineages has not been explored. Therefore, we sought to compare the virulence levels among CHIKV lineages, as well as to evaluate the cross-protective efficacy of the CHIKV/IRESv1 vaccine candidate, in two different models of CHIKV infection. Our results suggest that, although significant differences in virulence were observed among CHIKV lineages, the CHIKV/IRESv1 vaccine elicits cross-lineage protective immunity. These findings provide valuable information for predicting the severity of CHIKV-associated morbidity in future outbreaks, as well as vaccine development considerations.