Is bird flu worse than ever?

With a long history of cycling between catastrophic outbreaks and tentative lulls, bird flu is back, and threatens to be worse than ever.

Perhaps the main reason that bird flu has been such a successful disease is down to antigenic shift. Bird flu uses two antigens for entry into a host cell: hemagglutinin (H) and neuraminidase (N). There are currently 16 known H subtypes, and 9 known N subtypes. It is through cycling between these subtypes that bird flu is constantly able to change and adapt, preventing host species from building up resistance to it. For example, the 2013 outbreak saw the H7N9 strain to be dominant, whereas the 2000 outbreak saw it be replaced by H5N8.

The current outbreak is dominated by the H5N1 strain, which has several adaptations that allow it to pass easily from wild to domestic birds and vice versa. This gives it the potential to be the worst outbreak we have seen, facilitating a rapid spread around the globe. In the UK alone, there have been over 50,000 birds dead since October 2021.

Having reached Antarctica for the first time, the isolated populations of seals and penguins on Bird Island are particularly vulnerable. These populations have never encountered any variant of the disease, so have had no opportunity to build up any prior resistance. It is thought it was picked up by migratory birds from South America, and until we know the potential future consequences, any work involving animal handling has been suspended for fear of facilitating the spread.

Another highly devastated area is Bass Rock, home to the largest single colony of Northern Gannets in the world. Since 2021, there has been a 71% reduction in the number of occupied sites, and a 66% reduction in breeding success. However, there are some encouraging signs amid this deadly outbreak. In June 2022, a team led by Jude Lane from the RSPB noticed that some individuals in Bass Rock had black irises, as opposed to the common blue.

When these birds were taken for serological testing, it was demonstrated that the individuals with black irises were 78% more likely to come up positive for H5 antibodies in the blood, indicating that they had been previously infected by bird flu, but were now resistant. Not only is this the first documented case of resistance in sea birds, but it also provides a powerful, non-invasive diagnostic tool. Should this phenomenon apply to other species, it has the potential to revolutionise the way in which outbreaks are monitored.

“This has been a fascinating development and the discovery may prove a useful non-invasive diagnostic tool. The next steps are to understand its efficacy, if it applies to any other species and whether there are any detrimental impacts to the birds’ vision.”

Jude Lane, RSPB

The rate at which the virus is spreading calls for scientists to come up with innovative ways of controlling the disease, as simple culling methods will very soon become unsustainable, and vaccinations have little efficacy given the rapid evolution of the virus. This urgency has prompted scientists to look into genetic engineering as a potential solution.

By inducing small mutations to the ANP32A gene, scientists have been able to produce genetically engineered chickens with a 90% resistant rate when exposed to a typical dose of the virus. The ANP32A gene encodes for a protein that the virus can hijack in order to facilitate replication inside the cell. By mutating the gene for this protein, the scientists were able to change its shape, thus inhibiting this deadly interaction with the virus. This marks a promising step towards permanent disease resistance.

Despite this success, we are still met with the problem of the rapid evolutionary rate of the virus. Once the ANP32A protein was rendered useless in genetically modified chickens, we saw evidence of the viruses mutating in retaliation, coming up with strategies to instead hijack the ANP32B and ANP32E proteins. Nonetheless, we now have the tools to combat these changes, and there are plans to experimentally mutate these proteins to once again curb the interaction.

In conclusion, we are in the midst of a highly deadly outbreak of bird flu, which is spreading further and faster than ever before. Despite this, we are seeing some promising advancements in our ability to detect and prevent the disease, and our technology has never been more capable of halting the fatal progression.

Image description: The blue iris of a gannet

Image credit: Dean Eades, via BirdMad