Muthuraj Philma Glora, Pattnaik Aryamav, Sahoo Prakash K, Islam Md Torikul, Pattnaik Asit K, Byrareddy Siddappa N, Hanson Corrine, Anderson Berry Ann, Kachman Stephen D, Natarajan Sathish Kumar
Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Biomedicines. 2021 Jun 4;9(6):643. doi: 10.3390/biomedicines9060643.
Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.
孕期感染寨卡病毒（ZIKV）与胎儿小头畸形、宫内生长受限及眼部损伤的发生有关。ZIKV感染胎盘在从母体循环垂直传播至胎儿的过程中起关键作用。我们之前的研究表明，ZIKV可诱导内质网（ER）应激及胎盘滋养层细胞凋亡。在此，我们发现棕榈油酸酯（一种ω-7单不饱和脂肪酸）可预防ZIKV诱导的胎盘滋养层细胞内质网应激及凋亡。使用了人滋养层细胞系（JEG-3和JAR）及正常永生化滋养层细胞（HTR-8）。我们观察到，滋养层细胞感染ZIKV会导致凋亡，而用棕榈油酸酯处理ZIKV感染的细胞可显著预防凋亡。然而，棕榈酸（饱和脂肪酸）并不能保护细胞免受ZIKV诱导的内质网应激及凋亡。我们还观察到，与未用棕榈油酸酯处理的感染细胞相比，用棕榈油酸酯处理的ZIKV感染细胞中寨卡病毒RNA拷贝数减少，细胞活力提高。此外，棕榈油酸酯可保护胎盘滋养层细胞免受ZIKV诱导的内质网应激标志物、C/EBP同源蛋白及X盒结合蛋白-1剪接上调的影响。总之，我们的研究表明，棕榈油酸酯可保护胎盘滋养层细胞免受ZIKV诱导的内质网应激及凋亡。
