Probing proteins to assess pandemic risk
Mapping every possible change to a single protein reveals how flu viruses can make the jump from birds to humans.
Viruses copy themselves by hijacking the cells of an infected host, but this comes with some limitations. Cells from different species have different molecular machinery and so viruses often have to specialize to a narrow group of species. This specialization consists largely of fine-tuning the way that viral proteins interact with host proteins.
For instance, in bird flu viruses, a protein known as PB2 does not interact well with the machinery in human cells. Because PB2 proteins form part of the viral polymerase (the structure that copies the viral genome), this prevents bird flu viruses from replicating efficiently in humans. Sometimes however, changes in the PB2 protein allow bird flu viruses to better replicate in humans, potentially leading to deadly flu pandemics.
To understand exactly how this happens, researchers have previously used two approaches: examining the changes that have happened in past flu viruses, and monitoring the evolution of bird flu viruses grown in human cells in the lab. However, these approaches can only look at a small number of the many possible genetic changes to the virus. This makes it hard to anticipate the new ways that flu might adapt to human cells in the future.
To overcome this problem, Soh et al. systematically created all of the single changes to the bird flu PB2, altering every element of the protein sequence one-by-one. They then tested which of the changes to PB2 helped the virus grow better in human cells. The modifications that made the viruses thrive were on the surface of the protein, suggesting that they might improve interaction with the cell machinery of the host. Some changes have been found in bird flu viruses that have recently jumped into humans in nature, although fortunately none of these viruses have yet spread widely to cause a pandemic.
Many factors affect the evolution of viruses, and their ability to infect new species. Understanding which changes in proteins help these microbes adapt to new hosts is an important element that scientists could consider to assess future risks of pandemics.
Originally published at https://elifesciences.org/digests/45079.
