Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice.

Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice.
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DOI:
10.1371/journal.pntd.0005704
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发表时间:
2017-07
影响因子:
3.8
通讯作者:
Hewson R
Hewson R
中科院分区:
医学2区
文献类型:
--
作者:
Dowall SD;Graham VA;Rayner E;Hunter L;Atkinson B;Pearson G;Dennis M;Hewson R

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寨卡病毒(ZIKV)分为两个谱系:非洲谱系(ZIKVAF)和亚洲谱系(ZIKVAS)。尚未使用动物模型系统对这些谱系在疾病进展方面进行全面的平行测试。在此,利用已建立的I型干扰素受体敲除(A129)小鼠模型,首次证明ZIKVAF会导致致命感染,且根据攻毒剂量不同,疾病表现的动力学也不同。用10个空斑形成单位(pfu)低剂量攻毒的动物比用高5个对数剂量攻毒的动物出现更多的神经症状。相比之下,用ZIKVAS攻毒的动物即使在10⁶ pfu的剂量下也没有表现出临床症状或死亡。然而,在感染了两个谱系的ZIKV毒株的动物组织中都检测到了病毒RNA,并且观察到了相似的组织学变化。本研究强调了在寨卡病毒小鼠模型中非洲谱系和亚洲谱系之间毒株特异性的毒力差异。 自1947年首次被发现以来,寨卡病毒(ZIKV)主要与一种症状包括轻度发热和皮疹的轻症疾病相关。2007年,该病毒从非洲和亚洲传播到密克罗尼西亚,然后在2013年传播到法属波利尼西亚,接着跨越太平洋地区并传入南美洲。在这些新的地区,ZIKV与更严重的临床病症相关,包括吉兰 - 巴雷综合征(GBS)和先天性寨卡综合征。使用I型干扰素受体缺陷的小鼠品系(A129),通过类似于蚊子叮咬的自然感染途径用ZIKV攻毒后,我们比较了ZIKV的两个主要谱系:非洲谱系(ZIKVAF)和亚洲谱系(ZIKVAS)。虽然已知ZIKVAF会在A129小鼠中导致致命疾病,但我们观察到ZIKVAS引起的是非致命感染。为了证实这一发现,还对一株近期分离的ZIKVAS进行了评估,结果显示了相同的情况。我们的研究为小动物模型中ZIKV感染的机制提供了新的见解;并且可能有助于阐明该病毒引起的不同病理。
Zika virus (ZIKV) falls into two lineages: African (ZIKVAF) and Asian (ZIKVAS). These lineages have not been tested comprehensively in parallel for disease progression using an animal model system. Here, using the established type-I interferon receptor knockout (A129) mouse model, it is first demonstrated that ZIKVAF causes lethal infection, with different kinetics of disease manifestations according to the challenge dose. Animals challenged with a low dose of 10 plaque-forming units (pfu) developed more neurological symptoms than those challenged with 5-log higher doses. By contrast, animals challenged with ZIKVAS displayed no clinical signs or mortality, even at doses of 106 pfu. However, viral RNA was detected in the tissues of animals infected with ZIKV strains from both lineages and similar histological changes were observed. The present study highlights strain specific virulence differences between the African and Asian lineages in a ZIKV mouse model. Since first being recognised in 1947, Zika virus (ZIKV) has mainly been associated with a mild illness with symptoms including a limited fever and rash. In 2007 the virus spread from Africa and Asia into Micronesia, then in 2013 into French Polynesia and then onwards across Pacific regions and into South America. In these new regions, ZIKV has been associated with more severe clinical conditions including Gullain-Barre syndrome (GBS) and congenital Zika syndrome. Using a mouse strain with a deficiency in the type-I interferon receptor (A129), after challenge with ZIKV using a route that resembles the natural route of infection via mosquito bite we compared the two major lineages of ZIKV: African (ZIKAAF) and Asian (ZIKVAS). Whilst it was known that ZIKVAF causes a lethal disease in A129 mice, we observed a non-lethal infection with ZIKVAS. To confirm the finding, a recent isolate of ZIKVAS was additionally assessed and demonstrated the same observations. Our studies provide new insights into the mechanisms of ZIKV infection in a small animal model; and may help to elucidate the different pathologies caused by this virus.
DOI: 10.1371/journal.pntd.0004658
发表时间: 2016-05
影响因子: 3.8
作者:
Dowall SD;Graham VA;Rayner E;Atkinson B;Hall G;Watson RJ;Bosworth A;Bonney LC;Kitchen S;Hewson R
通讯作者: Hewson R
DOI: 10.1038/srep34793
发表时间: 2016-10-07
期刊: Scientific reports
影响因子: 4.6
作者:
Huang WC;Abraham R;Shim BS;Choe H;Page DT
通讯作者: Page DT
DOI: 10.1017/s0022172400025997
发表时间: 1979-01-01
期刊: JOURNAL OF HYGIENE
影响因子: --
作者:
FAGBAMI, AH
通讯作者: FAGBAMI, AH
DOI: 10.1126/science.aah6157
发表时间: 2016-09-09
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Abbink P;Larocca RA;De La Barrera RA;Bricault CA;Moseley ET;Boyd M;Kirilova M;Li Z;Ng'ang'a D;Nanayakkara O;Nityanandam R;Mercado NB;Borducchi EN;Agarwal A;Brinkman AL;Cabral C;Chandrashekar A;Giglio PB;Jetton D;Jimenez J;Lee BC;Mojta S;Molloy K;Shetty M;Neubauer GH;Stephenson KE;Peron JP;Zanotto PM;Misamore J;Finneyfrock B;Lewis MG;Alter G;Modjarrad K;Jarman RG;Eckels KH;Michael NL;Thomas SJ;Barouch DH
通讯作者: Barouch DH