An “immigration checkpoint” for viral entry and how influenza outsmarts it
(DOI: https://doi.org/10.1038/s44319-026-00942-x)
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Viruses are master manipulators which hijack cellular machinery to invade host cells, replicate, and release their progeny virions into the environment. This study, published in EMBO Reports by Gupta et al., reveals a previously unrecognized mechanism by which influenza virus gains entry into its target cells and bypasses the checkpoints that restrict it. The study finds that the WASH complex, which regulates endosomal actin dynamics, facilitates viral internalization in non-canonical manner. Intriguingly, while the WASH complex supports viral entry, its own FAM21 subunit acts as a molecular brake by linking WASH to the retromer subunit VPS35, thereby restraining its pro-endocytic activity. The host protein TRIM62 releases this brake by disrupting the WASH-retromer association, enabling WASH to function in a retromer-free state that favours productive viral entry. This discovery reveals a previously unknown molecular switch governing influenza entry and highlights a potential new avenue for host-directed antiviral strategies.