Flu Virus Exploits Immune System Weakness to Infect Cells

Most influenza viruses enter animal or human cells through particular surface-based pathways. Researchers at the University of Zurich have recently found that some human and avian influenza viruses can also enter cells through a second entry point involving an immune system protein complex. This feature aids in the viruses' ability to spread to other species and possibly even between humans and animals.

Most type A influenza viruses that are currently plaguing pigs and birds do not typically pose a threat to human health. Nevertheless, the viruses might be dangerous during seasonal epidemics or in the event of an outbreak similar to the one that is currently affecting dairy cattle in the US. Rarely a virus can spread from animals to people, which could have disastrous effects like a worldwide pandemic.

Additional Receptor Offers Alternative Entry Pathway

Most type A influenza viruses use their envelope proteins, which protrude from the surface like spikes, to enter host cells. The chemical group sialic acid, present on the surface of both human and animal cells, is bound by the so-called hemagglutinin.

It has now been demonstrated by an international research team headed by Professor Silke Stertz of the University of Zurich's (UZH) Institute of Medical Virology that flu viruses also possess a second way of infecting host cells.

Human influenza A viruses of subtype H2N2 and related H2N2 avian influenza viruses can enter cells through a second receptor. They use an alternative entry pathway.”

Silke Stertz, Research Head and Professor, Institute of Medical Virology, University of Zurich

Researchers have shown that Hemagglutinin also binds to MHC class II protein complexes. The ability to distinguish between native and foreign cells in the body is provided by these complexes on the surface of specific immune and respiratory cells.

We found that MHC class II complexes in humans, pigs, ducks, swans, and chickens allow viruses to enter cells, but not those in bats.”

Silke Stertz, Research Head and Professor, Institute of Medical Virology, University of Zurich

Transmission From Animals to Humans Likely

Both human airway cultures and lab-grown cell lines showed this dual capacity for infection. The degree of infection, host species, and infected tissues are largely determined by how well the viral receptor attaches to the cell surface structures. Receptor specificity also affects a virus's ability to infect humans or other animal species (zoonosis).

“Our finding shows that influenza viruses can adapt to different entry pathways. This might influence their ability to infect different species and potentially jump between animals and humans,” emphasized the UZH virologist.

Thus, there may be a higher chance than previously thought that swine, avian, and other animal influenza viruses could start a global flu pandemic in humans.

One of the possible causes of the 1957 H2N2 influenza pandemic in Asia could have been the virus's capacity to utilise MHC class II proteins for cell entry. This serves as more justification for increasing worldwide influenza surveillance for humans and animals.