Study Reveals Influenza Viruses Use Dual Pathways to Infect Cells

Researchers at the University of Zurich have uncovered a crucial insight into how influenza viruses infect cells, potentially increasing their risk of crossing species barriers and causing pandemics.

Their study, led by Professor Silke Stertz from the Institute of Medical Virology, reveals that certain human and avian influenza viruses may exploit a second entry mechanism into host cells, aside from the well-known route involving envelope proteins.

Typically, influenza viruses enter host cells by using spike-like envelope proteins called hemagglutinins, which bind to sialic acid on the surface of cells. However, this new research shows that some influenza viruses can also utilize MHC class II protein complexes, which are involved in the immune response and found on specific immune and respiratory cells. This discovery highlights a dual mechanism for viral entry: one through sialic acid and another through MHC class II complexes.

The study demonstrates that human influenza A viruses of subtype H2N2, along with related avian strains, can infect cells using both methods. Notably, this alternative entry pathway is observed in cells from humans, pigs, ducks, swans, and chickens, but not in bats. This dual entry capability allows these viruses to adapt and potentially infect different species, increasing the risk of zoonotic transmission—where viruses jump from animals to humans.

While most type A influenza viruses from birds and pigs are not considered major health threats to humans, their potential to cause pandemics remains significant. For instance, the current outbreak in dairy cattle in the U.S. and previous seasonal epidemics underline the importance of monitoring such viruses. The ability of some influenza strains to use MHC class II proteins for cell entry could explain why certain influenza viruses, like the H2N2 strain from the 1957 pandemic in Asia, have managed to cause widespread outbreaks.

This groundbreaking research underscores the urgent need for enhanced global influenza surveillance in both animals and humans. Understanding these viral mechanisms can help in better predicting and mitigating the risk of future flu pandemics.

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