Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane

Tong Chen, Aotian Ouyang, Jiahui Zou, Yi Feng, Changsong Wu, Meijun Jiang, Shaoyu Tu, Ling Ding, Yanqing Cheng, Wenshuo Hu, Wei Sheng, Yanglin Li, Meilin Jin, Huanchun Chen and Hongbo Zhou ()
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Tong Chen: Huazhong Agricultural University
Aotian Ouyang: Huazhong Agricultural University
Jiahui Zou: Huazhong Agricultural University
Yi Feng: Huazhong Agricultural University
Changsong Wu: Huazhong Agricultural University
Meijun Jiang: Huazhong Agricultural University
Shaoyu Tu: Huazhong Agricultural University
Ling Ding: Huazhong Agricultural University
Yanqing Cheng: Huazhong Agricultural University
Wenshuo Hu: Huazhong Agricultural University
Wei Sheng: Huazhong Agricultural University
Yanglin Li: Huazhong Agricultural University
Meilin Jin: Huazhong Agricultural University
Huanchun Chen: Huazhong Agricultural University
Hongbo Zhou: Huazhong Agricultural University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The molecular mechanisms underlying the transport of influenza A virus (IAV) membrane proteins to the cell surface remain largely unclear. In this study, siRNA screening identifies Rab27a as a critical host factor regulating this transport process. GTP-bound Rab27a operates via its effectors, synaptotagmin-like protein 1 (SYTL1) and SYTL4, to facilitate the transport of vesicles carrying viral membrane proteins to the plasma membrane. Absence of Rab27a or SYTL4 does not block the early stages of the IAV life cycle but restricts viral assembly and budding. Notably, silencing SYTL4 provides superior protection in the female mouse IAV infection model. This investigation elucidates the molecular mechanism by which Rab27a and its effectors modulate the transport of IAV membrane proteins, thereby bridging a critical gap in IAV life cycle research and presenting a potential target for the development of antiviral drugs.

Date: 2025
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DOI: 10.1038/s41467-025-61587-3

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