Possible Mechanisms in Bird Flu Viruses Facilitating Human Cell Infections

Avian flu virus may carry with them a bit of their bird origin, which could facilitate their adaptation to new hosts.

Generally, viruses can infect only specific types of hosts. For example, a number of viruses that infect humans are unable to infect other animals. However, influenza viruses frequently make the transition from birds to other species. In 2009, the H1N1, known as "swine flu", moved from birds to pigs and then to humans, setting off a pandemic. At present, there's a worldwide avian influenza outbreak infecting and killing birds, sea mammals, and some other animals. It's uncertain whether this flu virus will eventually infect humans and have the potential to spread easily and cause a pandemic.

Despite numerous cases of humans contracting bird flu, scientists were uncertain how these viruses manage to infect cells of different species. A recent study provides insight into one of the initial steps used by avian influenza viruses to adapt to infecting humans and other animals.

Researchers at the Chinese Academy of Agricultural Sciences in Harbin and their colleagues found that avian influenza viruses carry proteins that assist in their replication within their viral particles. The proteins, known as ANP32 proteins, might assist flu viruses in transitioning from birds to mammals, as per the report published on January 31 in Science Advances.

This discovery could enable researchers to better comprehend and predict which flu viruses can potentially cause a pandemic.

When viruses infect a host, they make use of elements already in the cell to aid in their replication, as they don't bring everything necessary with them, says Wendy Barclay, a molecular virologist at Imperial College London. While scientists knew that viruses came equipped with basic replication machinery named polymerases, that may not be sufficient to effectively establish an infection. The viruses need to commandeer host proteins – including ANP32 proteins – in order to rapidly replicate.

Avian influenza proteins within mammalian cells were inspected under electron microscopes by the researchers, revealing viral particles carrying a bit of bird ANP32. The researchers found out that this protein is likely attached to the viral polymerase and is packaged with the rest of the replication machinery into the viral particle. The higher the affinity between the polymerase and the ANP32 proteins, the more of these helper proteins are incorporated into viruses.

Scientists were unsure as to how avian influenza viruses, which have different ANP32 proteins than mammals, could connect with and utilize ANP32 proteins in human and other mammalian cells. It was suggested that some flu viruses may already have mutations that make it possible for viral polymerases to interact with mammalian ANP32 proteins. But the new study indicates that by storing their own bird versions of the proteins, flu viruses don't immediately need to harness host ANP32 proteins. Rather, the virus can use the avian ANP32 protein to make one round of copies inside the human or other animal cell.

The bird version of the polymerase may be able to interact with mammalian ANP32 proteins due to some mutations. Researchers found that viruses with the bird version of ANP32 were more likely to adapt mutations when grown in human cells or in mice. Jacob Yount, a viral immunologist at the Ohio State University College of Medicine in Columbus who was not involved in the research, says this could explain how avian viruses, which shouldn't be able to replicate in human cells, are indeed able to do so and evolve to interact with human ANP32

Barclay suggests investigators might be able to predict which viruses are more likely to cause a pandemic by evaluating the strength of interaction between the viral polymerase and ANP32, assuming these findings are verified by further investigation.