Zika virus (ZIKV) infection during pregnancy causes intrauterine growth defects and microcephaly, but knowledge of the mechanism through which ZIKV infects and replicates in the placenta remains elusive. Here, we found that ALPP, an alkaline phosphatase expressed primarily in placental tissue, promoted ZIKV infection in both human placental trophoblasts and astrocytoma cells. ALPP bound to ZIKV structural and nonstructural proteins and thereby prevented their proteasome-mediated degradation and enhanced viral RNA replication and virion biogenesis. In addition, the function of ALPP in ZIKV infection depends on its phosphatase activity. Furthermore, we demonstrated that ALPP was stabilized through interactions with BIP, which is the endoplasmic reticulum (ER)-resident heat shock protein 70 chaperone. The chaperone activity of BIP promoted ZIKV infection and mediated the interaction between ALPP and ZIKV proteins. Collectively, our findings reveal a previously unrecognized mechanism through which ALPP facilitates ZIKV replication by coordinating with the BIP protein.

中文翻译：

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胎盘碱性磷酸酶通过通过BIP稳定病毒蛋白来促进寨卡病毒复制。

妊娠期间感染寨卡病毒（ZIKV）会引起子宫内生长缺陷和小头畸形，但是对ZIKV感染胎盘和复制胎盘的机制的了解仍然不明确。在这里，我们发现ALPP（一种主要在胎盘组织中表达的碱性磷酸酶）促进了人胎盘滋养细胞和星形细胞瘤细胞中的ZIKV感染。ALPP与ZIKV结构和非结构蛋白结合，从而阻止了它们由蛋白酶体介导的降解，并增强了病毒RNA复制和病毒体的生物发生。此外，ALPP在ZIKV感染中的功能取决于其磷酸酶活性。此外，我们证明了ALPP是通过与BIP相互作用而稳定的，BIP是内质网（ER）驻留的热激蛋白70伴侣。BIP的伴侣活性促进ZIKV感染并介导ALPP和ZIKV蛋白之间的相互作用。总的来说，我们的发现揭示了ALPP通过与BIP蛋白配合促进ZIKV复制的机制。