数字农科院2.0

Newcastle disease virus exploits the phospholipid flippase ATP11c–CDC50A complex to promote viral infection

文献类型： 外文期刊

作者： Dandan Zhang;Yuechi Hou;Xusheng Qiu;Yang Qu;Yingjie Sun;Cuiping Song;Ying Liao;Chan Ding;Lei Tan

作者机构：

关键词： ATP11c–CDC50A complex;flippase;membrane asymmetry;Newcastle disease virus;phosphatidylserine;viral pathogenesis

期刊名称： Journal of Biological Chemistry

ISSN： 1083-351X

年卷期： 2025 年 301 卷 9 期

页码：

收录情况： SCIE（2025版） ; ; EI（2025版）

摘要： Newcastle disease virus (NDV), a highly contagious avian pathogen, causes significant economic losses in the poultry industry. As an enveloped, negative-sense single-stranded RNA virus, NDV infection and replication are intricately linked to host lipid metabolism, particularly phospholipids like phosphatidylserine (PS). PS asymmetry across the plasma membrane, maintained by phospholipid flippases, such as the ATP11c–CDC50A complex, is crucial for cellular homeostasis but can be exploited by viruses. However, the specific roles of PS and its dynamic regulation by flippases during NDV infection remain unclear. In this study, we investigated how NDV utilizes host PS and the ATP11c–CDC50A complex to facilitate its life cycle. We found that the phospholipid flippase ATP11c–CDC50A complex maintains membrane asymmetry by translocating PS to the inner leaflet, whereas NDV subverts this process by hijacking envelope-associated PS for viral entry and budding. CRISPR–Cas9-mediated ATP11c KO reduced PS flipping efficiency, impaired NDV replication, and disrupted progeny virion release. Notably, CDC50A mutations (D193G/K319E) compromised ATP11c activity, reducing PS redistribution by 60% (p < 0.05), highlighting its essential role in flippase function. Mechanistically, NDV-induced apoptosis triggered PS externalization, which enhanced matrix (M) protein clustering at PS-rich membrane domains, significantly increased virus-like particle production (p < 0.05). The results reveal that NDV exploits host ATP11c–CDC50A-mediated maintenance of inner-leaflet PS asymmetry to anchor M protein oligomerization at the plasma membrane during replication. These findings fundamentally advance our understanding of viral pathogenesis by elucidating how NDV subverts host lipid homeostasis to fuel its replication cycle.

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