Flu Viruses Use Different Molecular 'Doors' to Invade Human Lungs, Study Finds

A surprise discovery in a University of Vermont laboratory has upended a long-held assumption about how influenza infects people, revealing that different flu viruses use distinct molecular pathways to break into human lung cells — a finding that could open new avenues for desperately needed antiviral drugs.

The research, led by Emily Bruce, an assistant professor of microbiology and molecular genetics at UVM's Larner College of Medicine, found that the two main strains responsible for seasonal flu — H1N1 and H3N2 — do not enter cells in the same way. H3N2 depends on a cellular protein called Rab11B to establish infection, while H1N1 does not rely on it at all. The study was published in the Journal of Virology.

For decades, scientists largely assumed that influenza viruses gained entry by latching onto sialic acid, a sugar molecule on the surface of human cells, treating it as a universal binding point shared by all strains. Bruce's results challenge that view, showing that the route into the cell is more varied and strain-specific than previously recognized — a distinction researchers had not appreciated before.

"This study offers important new insights into how influenza viruses enter and interact with host cells," said Silke Stertz, a virologist at the University of Zürich who was not involved in the work. The discovery that different flu lineages exploit different host machinery suggests that the vulnerabilities of one strain may not apply to another, reshaping how scientists think about the basic biology of infection.

The practical stakes are significant. "We have very few antivirals for influenza or other viruses in general," Bruce noted, underscoring how thin the medical arsenal remains against a virus that sickens millions and kills tens of thousands each year. If specific proteins like Rab11B are essential for certain strains, they could become targets for new drugs designed to block infection at the door rather than after the virus has taken hold.

The finding lands against a backdrop of persistent flu activity; Vermont alone recorded 83 influenza outbreaks in settings such as schools and care facilities during the previous winter season. Bruce's team stumbled onto the distinction while pursuing a different question, a reminder that fundamental laboratory research can yield unexpected breakthroughs. Much work remains to map exactly how each strain commandeers human cells, but the study marks a meaningful step toward more targeted defenses against a virus that has long outpaced the treatments available to fight it.