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交叉反应性登革热病毒特异性 CD8 T 细胞可在怀孕期间预防寨卡病毒。

Cross-reactive Dengue virus-specific CD8 T cells protect against Zika virus during pregnancy.

机构信息

Division of Inflammation Biology, La Jolla Institute for Allergy & Immunology, 92037, La Jolla, CA, USA.

Department of Medicine, Molecular Microbiology, Pathology, and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, 63110, St. Louis, MO, USA.

出版信息

Nat Commun. 2018 Aug 2;9(1):3042. doi: 10.1038/s41467-018-05458-0.

Abstract

As Zika virus (ZIKV) emerges into Dengue virus (DENV)-endemic areas, cases of ZIKV infection in DENV-immune pregnant women may rise. Here we show that prior DENV immunity affects maternal and fetal ZIKV infection in pregnancy using sequential DENV and ZIKV infection models. Fetuses in ZIKV-infected DENV-immune dams were normal sized, whereas fetal demise occurred in non-immune dams. Moreover, reduced ZIKV RNA is present in the placenta and fetuses of ZIKV-infected DENV-immune dams. DENV cross-reactive CD8 T cells expand in the maternal spleen and decidua of ZIKV-infected dams, their depletion increases ZIKV infection in the placenta and fetus, and results in fetal demise. The inducement of cross-reactive CD8 T cells via peptide immunization or adoptive transfer results in decreased ZIKV infection in the placenta. Prior DENV immunity can protect against ZIKV infection during pregnancy in mice, and CD8 T cells are sufficient for this cross-protection. This has implications for understanding the natural history of ZIKV in DENV-endemic areas and the development of optimal ZIKV vaccines.

摘要

随着寨卡病毒(ZIKV)出现在登革热病毒(DENV)流行地区,DENV 免疫的孕妇感染 ZIKV 的病例可能会增加。在这里,我们使用连续的 DENV 和 ZIKV 感染模型表明,先前的 DENV 免疫会影响妊娠期间母体和胎儿的 ZIKV 感染。在 ZIKV 感染的 DENV 免疫母鼠中,胎儿大小正常,而在非免疫母鼠中则发生胎儿死亡。此外,在 ZIKV 感染的 DENV 免疫母鼠的胎盘和胎儿中存在减少的 ZIKV RNA。DENV 交叉反应性 CD8 T 细胞在 ZIKV 感染的母鼠的脾脏和蜕膜中扩增,其耗竭会增加胎盘和胎儿中的 ZIKV 感染,并导致胎儿死亡。通过肽免疫接种或过继转移诱导交叉反应性 CD8 T 细胞会导致胎盘中的 ZIKV 感染减少。先前的 DENV 免疫可以保护孕妇免受 ZIKV 感染,而 CD8 T 细胞是这种交叉保护所必需的。这对于理解 DENV 流行地区 ZIKV 的自然史以及开发最佳的 ZIKV 疫苗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6103/6072705/45095dc987f5/41467_2018_5458_Fig1_HTML.jpg

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