Yang Yanling, Wang Yuchen, Campbell Danielle E, Lee Heng-Wei, Beatty Wandy, Wang Leran, Baldridge Megan, López Carolina B
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Center for Women Infectious Disease Research, Washington University School of Medicine, St. Louis, Missouri, United States of America.
PLoS Pathog. 2025 Jan 10;21(1):e1012531. doi: 10.1371/journal.ppat.1012531. eCollection 2025 Jan.
Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed unknown critical roles for this factor in virus-cell and cell-to-cell fusion events for the different paramyxoviruses. While UGT was essential for virus-cell fusion during SeV entry to the cell, it was not required for NDV or MuV entry. Importantly, UGT promoted the formation of syncytia during MuV infection, suggesting a role in cell-to-cell virus spread. Our findings demonstrate that paramyxoviruses can bind to or enter A549 cells in the absence of canonical galactose-bound sialic-acid decorations and show that UGT facilitates paramyxovirus fusion processes involved in entry and spread.
副粘病毒是重要的人类和动物病原体，包括腮腺炎病毒（MuV）、新城疫病毒（NDV）和鼠副流感病毒仙台病毒（SeV）。尽管它们很重要，但已知与副粘病毒感染相关的宿主因子却很少。在功能丧失的CRISPR筛选中，我们使用表达不稳定eGFP的重组SeV（rSeVCdseGFP），确定了CMP-唾液酸转运体（CST）基因SLC35A1和UDP-半乳糖转运体（UGT）基因SLC35A2对副粘病毒感染至关重要。正如预期的那样，由于缺乏细胞表面唾液酸受体，SLC35A1基因敲除（KO）细胞对SeV、NDV和MuV的感染显著减少。然而，SLC35A2基因敲除细胞揭示了该因子在不同副粘病毒的病毒-细胞和细胞-细胞融合事件中的未知关键作用。虽然UGT在SeV进入细胞期间的病毒-细胞融合中是必需的，但NDV或MuV进入细胞时并不需要它。重要的是，UGT在MuV感染期间促进了多核体的形成，表明其在细胞间病毒传播中发挥作用。我们的研究结果表明，副粘病毒可以在没有典型的半乳糖结合唾液酸修饰的情况下与A549细胞结合或进入细胞，并表明UGT促进了副粘病毒参与进入和传播的融合过程。
