Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.
Biosensors (Basel). 2024 Jul 25;14(8):362. doi: 10.3390/bios14080362.
Orthoflaviviruses cause a major threat to global public health, and no antiviral treatment is available yet. Zika virus (ZIKV) entry, together with many other viruses, is known to be enhanced by phosphatidylserine (PS) receptors such as T-cell immunoglobulin mucin domain protein 1 (TIM-1). In this study, we demonstrate for the first time, using cell-based electrical impedance (CEI) biosensing, that ZIKV entry is also enhanced by expression of CD300a, another PS receptor. Furthermore, inhibiting CD300a in immature monocyte-derived dendritic cells partially but significantly inhibits ZIKV replication. As we have previously demonstrated that CEI is a useful tool to study Orthoflavivirus infection in real time, we now use this technology to determine how these PS receptors influence the kinetics of in vitro ZIKV infection. Results show that ZIKV entry is highly sensitive to minor changes in TIM-1 expression, both after overexpression of TIM-1 in infection-resistant HEK293T cells, as well as after partial knockout of TIM-1 in susceptible A549 cells. These results are confirmed by quantification of viral copy number and viral infectivity, demonstrating that CEI is highly suited to study and compare virus-host interactions. Overall, the results presented here demonstrate the potential of targeting this universal viral entry pathway.
黄病毒属对全球公共卫生构成重大威胁，但目前尚无抗病毒治疗方法。已知包括寨卡病毒（ZIKV）在内的许多病毒的进入都可通过磷脂酰丝氨酸（PS）受体（如 T 细胞免疫球蛋白黏蛋白结构域蛋白 1（TIM-1））得到增强。在这项研究中，我们首次通过基于细胞的电阻抗（CEI）生物传感技术证实，另一种 PS 受体 CD300a 的表达也可增强 ZIKV 的进入。此外，在未成熟单核细胞衍生的树突状细胞中抑制 CD300a 可部分但显著抑制 ZIKV 的复制。由于我们之前已经证明 CEI 是实时研究黄病毒属感染的有用工具，因此我们现在使用该技术来确定这些 PS 受体如何影响体外 ZIKV 感染的动力学。结果表明，ZIKV 的进入对 TIM-1 表达的微小变化非常敏感，无论是在感染抗性 HEK293T 细胞中过表达 TIM-1 后，还是在易感 A549 细胞中部分敲除 TIM-1 后均如此。通过对病毒拷贝数和病毒感染力的定量证实了这些结果，表明 CEI 非常适合用于研究和比较病毒-宿主相互作用。总的来说，这里呈现的结果表明靶向这种普遍的病毒进入途径具有潜力。
