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先天性寨卡综合征与干扰素阿尔法受体 1 有关。

Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

机构信息

Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.

Vice-Diretoria de Desenvolvimento Tecnológico, Instituto de Tecnologia em Imunobiológicos, Fiocruz, Rio de Janeiro, Brazil.

出版信息

Front Immunol. 2021 Nov 25;12:764746. doi: 10.3389/fimmu.2021.764746. eCollection 2021.

DOI:10.3389/fimmu.2021.764746
PMID:34899713
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8657619/
Abstract

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 () and interferon lambda 2 and 4 () single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; =0.032). No association between SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of and along with higher The rs2257167 CG/CC placentas also demonstrated high levels of and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.

摘要

影响先天性寨卡综合征 (CZS) 结局的宿主因素仍难以捉摸。干扰素已被报道为寨卡病毒和其他黄病毒感染的主要抗病毒因素。在这里，我们对 153 名孕妇（77 名未感染和 76 名感染 CZS）和 143 名新生儿（77 名未感染和 66 名感染 CZS）的样本进行了病例对照研究，以验证干扰素阿尔法受体 1 () 和干扰素 lambda 2 和 4 () 单核苷酸多态性 (SNP) 是否有助于 CZS 结局，并在足月时对胎盘基因表达谱进行了特征描述。携带 rs2257167 中 CG/CC 基因型的新生儿患 CZS 的风险更高（OR=3.41；IC=1.35-8.60；=0.032）。未观察到 SNPs 与 CZS 之间存在相关性。CZS 病例的胎盘表现出较低水平的 和 ，同时较高的 rs2257167 CG/CC 胎盘也表现出较高水平的 和炎症相关基因。我们发现 CZS 与足月时胎盘中 I 型 IFN 和 III 型 IFN 不足有关，形成了由 rs2257167 基因型调节的不平衡反应。尽管样本量较小，但这些发现揭示了宿主-病原体相互作用，重点是受基因调控的 I 型/III 型 IFN 轴，这可能导致更好地管理寨卡病毒和其他 TORCH（弓形虫、其他、风疹、巨细胞病毒、单纯疱疹）先天性感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/85d40db06a69/fimmu-12-764746-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/811c4af5e18e/fimmu-12-764746-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/d0cca63ee37a/fimmu-12-764746-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/a4ad2be64dc4/fimmu-12-764746-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/abbdad55c375/fimmu-12-764746-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/20aeb7d9b256/fimmu-12-764746-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/85d40db06a69/fimmu-12-764746-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/811c4af5e18e/fimmu-12-764746-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/d0cca63ee37a/fimmu-12-764746-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/a4ad2be64dc4/fimmu-12-764746-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/abbdad55c375/fimmu-12-764746-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/20aeb7d9b256/fimmu-12-764746-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/476b/8657619/85d40db06a69/fimmu-12-764746-g006.jpg

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