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Asian and African lineage Zika viruses show differential replication and innate immune responses in human dendritic cells and macrophages

机译:亚洲和非洲血统Zika病毒在人树突细胞和巨噬细胞中显示差异复制和先天免疫应答

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Zika virus (ZIKV) infections in humans are considered to be mild or subclinical. However, during the recent epidemics in the Pacific Islands and the Americas, the infection was associated with Quillain-Barré syndrome and congenital infections with fetal brain abnormalities, including microcephaly. Thus, more detailed understanding of ZIKV-host cell interactions and regulation of innate immune responses by strains of differential evolutionary origin is required. Here, we characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells (DCs) and macrophages. The epidemic Asian/American ZIKV replicated well and induced relatively good antiviral responses in human DCs whereas the African strain replicated less efficiently and induced weaker immune responses. In macrophages both the African and Asian strains showed limited replication and relatively weak cytokine gene expression. Interestingly, in macrophages we observed host protein degradation, especially IRF3 and STAT2, at early phases of infection with both lineage viruses, suggesting an early proteasomal activation in phagocytic cells. Our data indicates that ZIKV evolution has led to significant phenotypic differences in the replication characteristics leading to differential regulation of host innate immune responses.
机译:人类的Zika病毒(Zikv)感染被认为是轻度或亚临床。然而,在最近的太平洋岛屿和美洲的流行病中,感染与Quillain-Barré综合征和先天性感染有关,具有胎儿脑异常,包括微术。因此,需要更详细地了解Zikv-宿主细胞相互作用和通过差分进化原产株的菌株的原酸异常免疫应答的监管。在这里,我们的特征是由两个疫情亚裔/美国血管病毒引发的感染和免疫应答,包括来自胎儿大脑的分离物,以及人类单核细胞衍生的树突细胞(DCS)和巨噬细胞中的历史,低通过1947年的非洲血统病毒。疫情亚洲/美国Zikv复制良好,诱导人类DCS中的相对良好的抗病毒反应,而非洲菌株效率较低,诱导较弱的免疫应答。在巨噬细胞中,非洲和亚洲菌株都显示出有限的复制和相对较弱的细胞因子基因表达。有趣的是,在巨噬细胞中,我们观察到宿主蛋白质降解,特别是IRF3和Stat2,在血统病毒的早期感染阶段,表明吞噬细胞早期的蛋白酶体活化。我们的数据表明,Zikv Evolution导致复制特征的显着表型差异,导致主体先天免疫应答的差异调节。

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