tetano
Editor, Senior Moderator
PLoS Pathog
. 2025 Oct 10;21(10):e1013511.
doi: 10.1371/journal.ppat.1013511. Online ahead of print. TfR1 facilitates influenza virus endocytosis and uncoating by interacting with NA and M1 via extracellular and intracellular domains
Xinchen Wang[SUP] 1 2 3 4 [/SUP], Yuanhao Li[SUP] 1 2 3 4 [/SUP], Dezhong Ji[SUP] 1 3 4 [/SUP], Yiming Wang[SUP] 1 2 3 [/SUP], Xiaoyang Wang[SUP] 1 2 3 [/SUP], Kangming Guo[SUP] 1 2 3 [/SUP], Mengyang Wang[SUP] 1 2 3 [/SUP], Yu Mu[SUP] 2 [/SUP], Chen Qin[SUP] 3 [/SUP], Tao Yuan[SUP] 1 2 3 [/SUP], Yuanjie Zhang[SUP] 1 2 3 [/SUP], Zhiqian Chen[SUP] 1 2 3 [/SUP], Xingxing Zhu[SUP] 1 2 3 [/SUP], Xiaohui Zhang[SUP] 1 [/SUP], Honghui Jiang[SUP] 3 [/SUP], Qiuchen He[SUP] 1 2 [/SUP], Chuanling Zhang[SUP] 1 4 [/SUP], Sulong Xiao[SUP] 1 3 [/SUP], Lihe Zhang[SUP] 1 3 [/SUP], Demin Zhou[SUP] 1 2 3 4 [/SUP]
Affiliations
An intriguing enigma in virology is the utilization of transferrin receptor 1 (TfR1) by various viruses as an entry portal into host cells, a mechanism that remains relatively underexplored. In this study, we report a strategy to investigate the multifaceted aspects of viral entry, using Influenza A viruses (IAVs) as a model system. By decorating the sialylated viral envelope with photo-crosslinking moieties, we identify and elucidate the pivotal role of TfR1 in this process. Our results demonstrate that TfR1 initially functions as a receptor, interacting with the viral neuraminidase (NA) through its extracellular apical domain, thereby initiating viral endocytosis. Subsequently, TfR1 acts as a matrix degradator, engaging its intracellular stop-transfer sequence with the viral matrix protein 1 (M1), which in turn triggers proteasome- and aggresome-mediated nucleocapsid uncoating. The identification of the molecular interactions between TfR1 and NA, as well as the reciprocal degradation of TfR1 and M1 not only illuminates a cellular pathway that enriches our understanding of viral entry mechanisms but also presents exciting avenues for the development of innovative antiviral strategies beyond IAVs.
. 2025 Oct 10;21(10):e1013511.
doi: 10.1371/journal.ppat.1013511. Online ahead of print. TfR1 facilitates influenza virus endocytosis and uncoating by interacting with NA and M1 via extracellular and intracellular domains
Xinchen Wang[SUP] 1 2 3 4 [/SUP], Yuanhao Li[SUP] 1 2 3 4 [/SUP], Dezhong Ji[SUP] 1 3 4 [/SUP], Yiming Wang[SUP] 1 2 3 [/SUP], Xiaoyang Wang[SUP] 1 2 3 [/SUP], Kangming Guo[SUP] 1 2 3 [/SUP], Mengyang Wang[SUP] 1 2 3 [/SUP], Yu Mu[SUP] 2 [/SUP], Chen Qin[SUP] 3 [/SUP], Tao Yuan[SUP] 1 2 3 [/SUP], Yuanjie Zhang[SUP] 1 2 3 [/SUP], Zhiqian Chen[SUP] 1 2 3 [/SUP], Xingxing Zhu[SUP] 1 2 3 [/SUP], Xiaohui Zhang[SUP] 1 [/SUP], Honghui Jiang[SUP] 3 [/SUP], Qiuchen He[SUP] 1 2 [/SUP], Chuanling Zhang[SUP] 1 4 [/SUP], Sulong Xiao[SUP] 1 3 [/SUP], Lihe Zhang[SUP] 1 3 [/SUP], Demin Zhou[SUP] 1 2 3 4 [/SUP]
Affiliations
- PMID: 41071818
- DOI: 10.1371/journal.ppat.1013511
An intriguing enigma in virology is the utilization of transferrin receptor 1 (TfR1) by various viruses as an entry portal into host cells, a mechanism that remains relatively underexplored. In this study, we report a strategy to investigate the multifaceted aspects of viral entry, using Influenza A viruses (IAVs) as a model system. By decorating the sialylated viral envelope with photo-crosslinking moieties, we identify and elucidate the pivotal role of TfR1 in this process. Our results demonstrate that TfR1 initially functions as a receptor, interacting with the viral neuraminidase (NA) through its extracellular apical domain, thereby initiating viral endocytosis. Subsequently, TfR1 acts as a matrix degradator, engaging its intracellular stop-transfer sequence with the viral matrix protein 1 (M1), which in turn triggers proteasome- and aggresome-mediated nucleocapsid uncoating. The identification of the molecular interactions between TfR1 and NA, as well as the reciprocal degradation of TfR1 and M1 not only illuminates a cellular pathway that enriches our understanding of viral entry mechanisms but also presents exciting avenues for the development of innovative antiviral strategies beyond IAVs.