biostudies-literatureUnknownYu JNICHD NIH HHSZika virus (ZIKV) infection can lead to a variety of clinical outcomes, including severe congenital abnormalities. The phosphatidylserine (PS) receptors AXL and TIM-1 are recognized as critical entry factors for ZIKV <i>in vitro</i>. However, it remains unclear if and how ZIKV regulates these receptors during infection. In this study, we investigated AXL and TIM-1 expression in human alveolar basal epithelial A549 cells, glioblastoma U87 cells, and embryonic stem cells-derived trophoblast following ZIKV infection. We found that both the Asian strain FSS13025 and the African strain MR766 of ZIKV downregulate AXL, with a milder effect on TIM-1. We identified several ZIKV proteins, notably envelope (E), NS2A, NS3, and NS4B, that contribute to this downregulation. Notably, treatment with lysosbioRxiv : the preprint server for biology2024.12.31.630961https://www.ebi.ac.uk/biostudies/studies/S-EPMC11722360biostudies-literatureAutophagy-Mediated Downregulation of AXL and TIM-1 Promotes Sustained Zika Virus Infection.PMC11722360R01 HD094937Roberts RMSheridan MAEzashi TYu JZheng YMLiu SLfalseAutophagy-Mediated Downregulation of AXL and TIM-1 Promotes Sustained Zika Virus Infection.Zika virus (ZIKV) infection can lead to a variety of clinical outcomes, including severe congenital abnormalities. The phosphatidylserine (PS) receptors AXL and TIM-1 are recognized as critical entry factors for ZIKV <i>in vitro</i>. However, it remains unclear if and how ZIKV regulates these receptors during infection. In this study, we investigated AXL and TIM-1 expression in human alveolar basal epithelial A549 cells, glioblastoma U87 cells, and embryonic stem cells-derived trophoblast following ZIKV infection. We found that both the Asian strain FSS13025 and the African strain MR766 of ZIKV downregulate AXL, with a milder effect on TIM-1. We identified several ZIKV proteins, notably envelope (E), NS2A, NS3, and NS4B, that contribute to this downregulation. Notably, treatment with lysos2025-01-01T00:00:00Z2025 Jan2026-04-19T03:30:09.993Z2025-04-07T07:52:20.345ZS-EPMC117223603980353410.1101/2024.12.31.630961