Most influenza viruses get into human or animal cells through specific pathways on the cells’ surface. Recently, researchers have found that certain human flu viruses and avian flu viruses can also utilize a second entry pathway, a protein complex of the immune system, to infect cells. This capability helps the viruses infect different species and potentially move between animals and humans.
Most influenza viruses get into human or animal cells through specific pathways on the cells’ surface. Researchers at the University of Zurich have found that certain human flu viruses and avian flu viruses can also utilize a second entry pathway, a protein complex of the immune system, to infect cells. This helps the viruses infect different species and potentially cross between animals and humans.
The majority of type A influenza viruses circulating in birds and pigs usually aren’t a direct threat to humans. However, these viruses can become a concern during outbreaks like the current one in dairy cattle in the US or during seasonal epidemics. In rare situations, a virus can move from animals to humans, leading to severe consequences such as a global pandemic.
Additional receptor provides an alternative entry pathway
Most influenza viruses enter host cells by utilizing their envelope proteins, which stick out from the surface like spikes. The hemagglutinin binds to sialic acid, a chemical group on the surface of human cells and cells of various animal species. An international research team, headed by Professor Silke Stertz from the Institute of Medical Virology at the University of Zurich (UZH), has shown that flu viruses also possess a second way to infect host cells. “Human influenza A viruses of subtype H2N2 and related H2N2 avian influenza viruses can penetrate cells through a second receptor. They employ an alternate entry pathway,” explains Stertz.
The researchers discovered that hemagglutinin also attaches to MHC class II protein complexes. These complexes on certain immune and respiratory cells are crucial for distinguishing between the body’s cells and foreign cells. “We observed that MHC class II complexes in humans, pigs, ducks, swans, and chickens enable viruses to enter cells, but not in bats,” notes Stertz.
Likely transmission from animals to humans
This dual cell invasion ability was observed in lab-cultured cell lines and human airway cultures. The compatibility of the viral receptor with the cell surface structures is pivotal in determining which host species and tissues get infected and the severity of the infection. The receptor’s specificity also influences whether a virus can infect different animal species or even humans (zoonosis). “Our discovery indicates that influenza viruses can adapt to utilize diverse entry pathways. This could impact their ability to infect various species and potentially transfer between animals and humans,” stresses the UZH virologist.
The possibility of avian, swine, and other animal flu viruses causing a flu pandemic in humans may be higher than previously thought. The ability to use MHC class II proteins for cell entry might have been one of the factors why H2N2 influenza viruses emerged as a pandemic virus in Asia in 1957. This underscores the importance of enhancing global influenza monitoring in both animals and humans.
