When we are ill with a virus infection, it is because the virus has entered cells in our body and taken over their machinery to make copies of itself. Finding ways to disrupt this process is important for antiviral drug development. Now, a new study reveals how the flu virus relies on a protein in the host cell to help it complete its mission.
The researchers found that a host protein called ANP32A allows the flu virus to replicate in cells.

The study team – led by researchers at Imperial College London in the UK – reports the findings in the journal Nature and suggests they may lead to improvements in how we treat pandemic and seasonal flu, which infects over 800 million people worldwide every year.

Flu pandemics occur when an influenza or flu virus that has been circulating in bird populations undergoes a change that allows it to infect mammal cells. Otherwise, an avian flu virus cannot usually infect mammals.

Senior author Wendy Barclay, a professor at Imperial who specializes in influenza virology, says:

“All human flu viruses in the world originally came from birds. However, luckily for us, viruses don’t often jump from birds to people because the virus can’t replicate in our cells.”

Previous studies have shown there are a number of reasons avian flu viruses cannot easily replicate in human cells – mostly due to incompatibilities between virus components and the host cell.

One of these incompatibilities surrounds the activity of an enzyme – called RNA-dependent RNA polymerase – that is present in the avian virus and that it needs to replicate. The enzyme has “poor activity” in human cells, note the authors.

Host protein ANP32A helps flu virus replicate in cells

Prof. Barclay and colleagues decided to investigate what helps the flu virus replicate inside host cells in more detail by infecting hamster-chicken hybrid cells with avian flu virus and observing what happens.

They experimented with a range of hybrid cells made by inserting fragments of chicken DNA into hamster cells and then testing whether avian flu viruses were able to replicate inside them. The idea was that any cells that the virus can replicate in must contain the protein necessary for avian virus polymerase to do its work.

After observing which cells the avian flu virus replicated in, they analyzed which chicken genes were present and identified that a protein called ANP32A was responsible for allowing the virus to replicate.

Mammals also have a version of ANP32A, but it is much shorter than the avian protein, and avian flu viruses cannot use it unless they carry a particular mutation, note the authors.

The findings are important because they show the kind of change an avian flu virus has to undergo in order to jump from birds to humans.

Prof. Barclay sums up the study:

Up until now, we haven’t understood why the bird flu virus has to change in order to hijack the human cell machinery. Our research showed this is all due to a cell protein called ANP32A.”

She and her team also carried out further experiments and found that the human ANP32A protein was crucial to the seasonal flu virus replicating in human cells. When they removed the protein, it stopped virus infection.

The next stage would be to investigate treatments that could block this particular interaction between virus and host cells as a way to stop infection.

Meanwhile, Medical News Today recently reported how immune cells known to fight the flu in mice may also help fight respiratory syncytial virus (RSV) in the lungs. RSV is the main cause of the common cold. It is also one of the main reasons children are admitted to hospital, and the main cause of severe lung infection in older adults.