Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Neuronal Development, Center for Molecular Neurobiology Hamburg (ZNMH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nat Microbiol. 2018 Oct;3(10):1161-1174. doi: 10.1038/s41564-018-0236-1. Epub 2018 Sep 10.
Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.
先天性寨卡病毒（ZIKV）综合征可能导致受影响新生儿中约 1%的胎儿小头畸形。在这里，我们研究了大多数临床无症状的新生儿是否可能长期存在出生时不易察觉的健康损害。高剂量 ZIKV 感染免疫功能正常的怀孕小鼠导致了严重的后代表型，如胎儿死亡，这是预期的。相比之下，低剂量（LD）母体 ZIKV 感染导致胎儿出生体重减轻，但没有其他明显的表型。与雌性同窝仔相比，来自 LD ZIKV 感染母亲的雄性后代的睾丸酮（TST）水平升高，并且在宫内感染中更不可能存活。雄性后代的顶树突和基底树突中的不成熟神经元数量增加，而雌性后代仅在基底树突中有不成熟神经元。此外，高但不是非常高（风暴）TST 水平的雄性后代与女性相比，更有可能遭受学习和记忆障碍。未来的研究需要了解 TST 对以后生活中的神经病理学和神经认知障碍的影响。总之，在寨卡病毒流行率高的国家，需要对性别特异性进行更高的警惕，因为神经发育受损可能会被出生时的健康外观所掩盖。
