Human Sertoli cells support high levels of Zika virus replication and persistence.
Human Sertoli cells support high levels of Zika virus replication and persistence.
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DOI：
10.1038/s41598-018-23899-x
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发表时间：
2018-04-03
影响因子：
4.6
通讯作者：
Hobman TC
中科院分区：
文献类型：
--
作者：
Kumar A;Jovel J;Lopez-Orozco J;Limonta D;Airo AM;Hou S;Stryapunina I;Fibke C;Moore RB;Hobman TC
寨卡病毒是一种致畸性蚊媒黄病毒，与新生儿的出生缺陷和成人的格林-巴利综合征有关。该病毒也可以通过性传播，但目前对支持病毒在人类睾丸中复制和持续存在的细胞类型知之甚少。使用原代细胞培养物，我们观察到支持细胞而不是间质细胞对寨卡病毒感染高度敏感，这一过程依赖于TAM家族受体Axl。在细胞培养中，支持细胞可以用寨卡病毒有效感染至少6周。支持细胞的感染导致这些细胞的转录谱发生巨大变化。感染细胞中上调最多的mRNA是碱性成纤维细胞生长因子（FGF 2），这是一种被发现可以增强寨卡病毒复制并支持病毒持久性的细胞因子。这些发现为了解寨卡病毒如何在男性生殖道中持续存在提供了关键见解，反过来可能有助于开发抗病毒疗法或策略，以尽量减少这种病原体的性传播。
Zika virus is a teratogenic mosquito-transmitted flavivirus that is associated with birth defects in newborns and Guillain–Barré syndrome in adults. The virus can also be sexually transmitted, but currently, very little is known about the cell types supporting virus replication and persistence in human testes. Using primary cell cultures, we observed that Sertoli but not Leydig cells are highly susceptible to Zika virus infection, a process that is dependent on the TAM family receptor Axl. In cell culture, Sertoli cells could be productively infected with Zika virus for at least 6-weeks. Infection of Sertoli cells resulted in dramatic changes to the transcriptional profile of these cells. The most upregulated mRNA in infected cells was basic fibroblast growth factor (FGF2), a cytokine that was found to enhance Zika virus replication and support viral persistence. Together these findings provide key insights into understanding how Zika virus persists in the male reproductive tract and in turn may aid in developing antiviral therapies or strategies to minimize sexual transmission of this pathogen.
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