Mazzetto Eva, Bortolami Alessio, Bovo Davide, Stocchero Matteo, Mazzacan Elisa, Napolitan Alessandra, Panzarin Valentina, Tran Maria Rosa, Zamperin Gianpiero, Milani Adelaide, Fortin Andrea, Bigolaro Michela, Pirillo Paola, Pagliari Matteo, Zanardello Claudia, Giordano Giuseppe, Gervasi Maria Teresa, Baraldi Eugenio, Terregino Calogero, Giaquinto Carlo, Bonfante Francesco
Department of Women's and Children's Health, Padua University, Padova (PD), Italy; Department of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), Italy.
Department of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), Italy.
Virus Res. 2025 Feb;352:199518. doi: 10.1016/j.virusres.2024.199518. Epub 2025 Jan 6.
Among flaviviruses, Zika virus (ZIKV) is the only arbovirus officially recognized as a teratogenic agent, as a consequence of its ability to infect and cross the placental barrier causing congenital malformation in the fetus. While many studies have focused on understanding ZIKV pathogenesis during pregnancy, the viral mechanisms affecting fetal development remain largely unclear. In this study, we investigated ZIKV virulence in placental trophoblasts, using viruses with distinct lipid profiles. Firstly, we propagated a ZIKV strain belonging to the Asian lineage in either mammalian or mosquito cells, obtaining two viral stocks, which were purified and analyzed to determine their genetic and lipid composition. Successively, we assessed the infectivity of the two stocks in placental cells using both immortalized cell lines and explants. We found that the two viral stocks displayed identical consensus sequences with homogeneous quasispecies composition. However, the lipid composition of their envelope significantly varied depending on the cell of origin, with the mammalian-derived viral stock characterized by a higher content of phosphatidylcholines compared to the virions originating from mosquito cells. Notably, ZIKV stock derived from mammalian cells showed a higher infectivity in immortalized villous trophoblasts and full-term placental explants of human origin. This increased infectivity was linked to enhanced fusion efficiency during the viral uncoating phase in trophoblast cells, as demonstrated using a lipophilic probe. Collectively, our data suggest a potential role of viral lipids as determinants of ZIKV infectivity in full-term placenta, underscoring the importance of lipidomic research in virology.
在黄病毒属中，寨卡病毒（ZIKV）是唯一被官方认定为致畸原的虫媒病毒，因其能够感染并穿过胎盘屏障，导致胎儿先天性畸形。虽然许多研究致力于理解孕期寨卡病毒的发病机制，但影响胎儿发育的病毒机制仍不清楚。在本研究中，我们使用具有不同脂质谱的病毒，研究了寨卡病毒在胎盘滋养层细胞中的毒力。首先，我们在哺乳动物细胞或蚊细胞中培养了一株属于亚洲谱系的寨卡病毒，获得了两种病毒储备液，对其进行纯化和分析，以确定其基因和脂质组成。随后，我们使用永生化细胞系和外植体评估了这两种储备液在胎盘细胞中的感染性。我们发现，这两种病毒储备液具有相同的共有序列和均一的准种组成。然而，其包膜的脂质组成因来源细胞而异，与源自蚊细胞的病毒粒子相比，源自哺乳动物细胞的病毒储备液中磷脂酰胆碱的含量更高。值得注意的是，源自哺乳动物细胞的寨卡病毒储备液在人源永生化绒毛滋养层细胞和足月胎盘外植体中表现出更高的感染性。使用亲脂性探针证明，这种增强的感染性与滋养层细胞病毒脱壳阶段融合效率的提高有关。总体而言，我们的数据表明病毒脂质可能作为寨卡病毒在足月胎盘中感染性的决定因素，强调了脂质组学研究在病毒学中的重要性。
