AI Article Synopsis
- Influenza A virus primarily enters host cells through a process called clathrin-dependent receptor-mediated endocytosis, but the exact entry receptor has not been definitively identified.
- Researchers used a method involving proximity ligation and mass spectrometry to identify transferrin receptor 1 (TfR1) as a potential receptor that facilitates IAV entry.
- Experiments confirmed that TfR1's recycling is crucial for virus entry, and even modified forms of TfR1 can assist in IAV uptake, highlighting a unique mechanism by which the virus exploits the receptor.
Article Abstract
Influenza A virus (IAV) enters host cells mostly through clathrin-dependent receptor-mediated endocytosis. A single bona fide entry receptor protein supporting this entry mechanism remains elusive. Here we performed proximity ligation of biotin to host cell surface proteins in the vicinity of attached trimeric hemagglutinin-HRP and characterized biotinylated targets using mass spectrometry. This approach identified transferrin receptor 1 (TfR1) as a candidate entry protein. Genetic gain-of-function and loss-of-function experiments, as well as in vitro and in vivo chemical inhibition, confirmed the functional involvement of TfR1 in IAV entry. Recycling deficient mutants of TfR1 do not support entry, indicating that TfR1 recycling is essential for this function. The binding of virions to TfR1 via sialic acids confirmed its role as a directly acting entry factor, but unexpectedly even headless TfR1 promoted IAV particle uptake in . TIRF microscopy localized the entering virus-like particles in the vicinity of TfR1. Our data identify TfR1 recycling as a revolving door mechanism exploited by IAV to enter host cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214170 | PMC |
| http://dx.doi.org/10.1073/pnas.2214936120 | DOI Listing |
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