Pre-eclampsia (typically characterized by new-onset hypertension and proteinuria in the second half of pregnancy) represents a major determinant of the global burden of disease1,2. Its pathophysiology involves placental dysfunction, but the mechanism is unclear. Viral infection can cause organ dysfunction, but its role in placentally related disorders of human pregnancy is unknown3. We addressed this using RNA sequencing metagenomics4-6 of placental samples from normal and complicated pregnancies. Here, we show that human herpesvirus 6 (HHV-6, A or B) RNA was detected in 6.1% of cases of pre-eclampsia and 2.2% of other pregnancies. Fetal genotyping demonstrated that 70% of samples with HHV-6 RNA in the placenta exhibited inherited, chromosomally integrated HHV-6 (iciHHV-6). We genotyped 467 pre-eclampsia cases and 3,854 controls and found an excess of iciHHV-6 in the cases (odds ratio of 2.8, 95% confidence intervals of 1.4-5.6, P = 0.008). We validated this finding by comparing iciHHV-6 in a further 740 cases with controls from large-scale population studies (odds ratio of 2.5, 95% confidence intervals of 1.4-4.4, P = 0.0013). We conclude that iciHHV-6 results in the transcription of viral RNA in the human placenta and predisposes the mother to pre-eclampsia.

中文翻译：

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染色体整合的人类疱疹病毒 6 的胎儿遗传使母亲易患先兆子痫。

先兆子痫（通常以妊娠后半期新发高血压和蛋白尿为特征）是全球疾病负担的主要决定因素1,2。其病理生理涉及胎盘功能障碍，但机制尚不清楚。病毒感染可引起器官功能障碍，但其在人类妊娠胎盘相关疾病中的作用尚不清楚3。我们使用来自正常和复杂妊娠的胎盘样本的 RNA 测序宏基因组学 4-6 解决了这个问题。在这里，我们表明在 6.1% 的先兆子痫病例和 2.2% 的其他妊娠病例中检测到人类疱疹病毒 6（HHV-6、A 或 B）RNA。胎儿基因分型表明，胎盘中 70% 的 HHV-6 RNA 样本表现出遗传性、染色体整合的 HHV-6 (iciHHV-6)。我们对 467 例先兆子痫病例和 3 例进行了基因分型，854 名对照者发现病例中 iciHHV-6 过量（比值比为 2.8，95% 置信区间为 1.4-5.6，P = 0.008）。我们通过将另外 740 个病例中的 iciHHV-6 与大规模人口研究的对照进行比较来验证这一发现（比值比为 2.5，95% 置信区间为 1.4-4.4，P = 0.0013）。我们得出结论，iciHHV-6 导致人类胎盘中病毒 RNA 的转录，并使母亲易患先兆子痫。