TfR1 facilitates influenza virus endocytosis and uncoating by interacting with NA and M1 via extracellular and intracellular domains.

ABSTRACT: 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 prote

SUBMITTER: Wang X 

PROVIDER: S-EPMC12533913 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature