Emily Bruce, assistant professor of microbiology and molecular genetics, at the University of Vermont in Burlington in April 2026. File photo by Glenn Russell/VTDigger It was by accident that Emily Bruce’s lab upended a long-held understanding of how the flu virus infects humans and stumbled a cross a finding that could set the stage for better prevention. That chance discovery evolved into a paper out this week in the Journal of Virology that details how different flu viruses enter and infect human lungs in distinct ways.  Bruce, an assistant professor of microbiology and molecular genetics at the University of Vermont’s Larner College of Medicine, originally set out with her lab to look at how specific proteins within two flu viruses move and replicate.  The way Bruce explains it, it’s actually quite simple: The two primary seasonal flu viruses — H1N1 and H3N2 — are often treated interchangeably in flu tests and in clinical treatments. In naming influenza viruses, the “H” stands for hemagglutinin, a protein on the surface of the virus that enables its entrance to a cell, while the “N” stands for neuraminidase, a protein that cuts the virus away from its host cell, allowing it to go on to infect the next cell.  Bruce’s research team soon noticed a particular protein, Rab11B, was fundamental to the infectiousness of H3N2. In human cells with low levels of that protein, the H3N2 virus couldn’t enter or replicate in a human lung. H1N1 had no such problem.  Bruce’s lab then sequenced different pieces of the viral genome from a cell of a Vermonter infected with flu in 2022. They isolated the role Rab11B plays in the virus’s entry to the lung protein.  For years, the prevailing dogma was that sialic acid — a sugar all over the surface of all kinds of proteins in human cells — was like a universal binding point that an influenza virus attaches itself to in humans, according to Bruce. But when her lab removed the Rab11B protein in human cells, the H3N2 strains couldn’t get in anymore — even if sialic acid was there waiting for something to bind.   In humans, those Rab11B proteins transport other cellular proteins to the right place at the right time, Bruce said. Without it, the proteins are not in the place they need to be for the H3N2 virus to bind.  Having this tighter view on what paves the path to infection can eventually lead to more directed antiviral research, Bruce said.  “We have very few antivirals for influenza or other viruses in general,” she said, noting the omnipresence of that sialic acid and its widely understood role in binding. “That inherently makes it something that doesn’t sound like a very good target for a drug, because it’s kind of expressed everywhere on everything.”  A human lung cell infected with influenza. The viral nucleoprotein is in red, a cellular protein highjacked by influenza is in green, and the cell’s nucleus is in blue. Image courtesy of Emily Bruce’s lab But with new understanding, that could change.  Silke Stertz is a professor of medical virology at the University of Zürich in Switzerland whose research overlaps with Bruce’s. She’d seen Bruce’s findings presented at a conference and found them exciting, she told VTDigger. “This study offers important new insights into how influenza viruses enter and interact with host cells. Particularly noteworthy is the finding that H1N1 and H3N2 viruses appear to use different routes to enter cells, revealing a distinction that had not been recognized before,” Stertz wrote in an email. Silke added that the deeper understanding of how these viruses enter host cells is particularly valuable to help guide the development of new antiviral treatments. Emily Mosites, the epidemiologist for infectious diseases at the Vermont Health Department, echoed Stertz’s enthusiasm for the finding. “This new molecular research gives us further insight into how these infections occur,” she wrote in a statement to VTDigger.  Mosites added that flu remains a crucial public health concern in Vermont, especially in winter months. Last year’s flu season was particularly grueling. Mosites said Vermont saw 83 influenza outbreaks in settings like long-term care facilities and schools last winter. Read the story on VTDigger here: One UVM lab’s surprise discovery led to flu science breakthrough. ...read more read less