Study unveils the evolution of a deadly bird flu

Published online 2 March 2024

Gene exchange between the bird flu variant in Egypt gave rise to a new fatal strain that evolved in Europe and spread through wild birds across the world

Mohamed Mansour

Credit: Martin Bernetti/AFP via Getty

A recent study in Nature has uncovered the ecological and viral underpinnings of the global spread of a subtype of avian flu strain (H5N1), which in 2021 mutated through wild birds in Europe and has killed millions of birds across five of the seven continents in 2022.In the first six months of 2022, more than 69 million farmed birds were culled, and 34,000 wild birds died from the virus, though the authors argue that the wild bird tally is significantly underestimated. The study tracks the evolution of the H5N1 virus and analysed 10,000 viral genomes to detect its genomic evolution and how it spread so widely and became so deadly for wild birds, despite its emergence as a poultry pathogen. They studied data reported to the UN Food and Agricultural Organization as well as to the World Organization for Animal Health between 2005 and 2022.  The team of international researchers revealed that it mutated to spread three times faster among wild birds than it did between farmed poultry in 2020, and has caused a significant rise in incidental infections in wild carnivores, mink, and marine mammals. The researchers concluded that there is a shift in the highly pathogenic avian influenza (HPAI) H5 subtype’s epicentre that goes beyond Asia, where it first emerged in 1996, and indicate that the spread of the virus in wild birds is facilitating geographic and host range expansion. Earlier strains were caused by more stable genomic constellations but have since adapted through the domestic-wild bird interface. The virus spread in 2005 through migratory birds coming from China to Egypt, where it was declared an epidemic in 2006. Egypt declared an epidemic in 2006, when “that voracious variant wiped out entire farms, and infected about 359 humans,” says Rabeh Al-Shishini, virologist at Egypt’s National Research Centre (NRC), and co-author of the study. At the time, Egypt began vaccinating poultry with vaccines against that avian influenza subvariant, but it became endemic in Egypt until 2017, when poultry and wild birds were infected with another bird flu subvariant called H5N8 that further caused a global spike in 2020 and 2021.“The 2016 and 2017 outbreak in Egypt is attributable to multiple reasons, including the absence of effective vaccines against the prevailing bird flu variants,” says Al-Shishini. The newest H5N1 strain taking over the world has evolved from, and almost entirely replaced, the H5N8 stain that emerged in Egypt in 2016. The current outbreak is caused by two subtypes; one that spread in the northern coastal regions of central Europe and then on to North America by migrating birds, and the other in the Mediterranean Sea and subsequently in Africa.  The mutations and widespread between species led researchers to explore not just the origins, but also the factors that led to the mutation of the new variant.

Better understanding for tighter control

Influenza viruses are fragmented-genome viruses, meaning that their genetic material exists as multiple, separate parts, rather than a single coherent strand of genetic material. When two different variants of influenza viruses infect the same host, the fragmented genomes of the two variants can mix and exchange genetic material to form a new variant combining their characteristics. This can occur in humans and animals alike, especially when different variants of the same virus become prevalent.During reassortment, parts of one variant can combine with parts of another, resulting in new viral variants that may have altered characteristics, for which humans or animals have little prior immunity. This genetic recombination may lead to the emergence of a viral subvariant that can cause a global pandemic, and infect a new host that the original variant wouldn’t infect, Al-Shishini explains. Understanding these variants is vital for detecting the spread and evolution of the virus, and for designing vaccines, and developing strategies to manage and control the virus, says Richard Webby, virologist at St. Jude Children’s Research Hospital, who has been studying virus-host interactions for more than a decade.Many bird flu outbreaks start in poultry, explains Webby, a co-author of the study. But transmission to wild birds means spread of the virus at a wider scale, creating a global challenge that is hard to manage. “That is why we always seek to discover the origins and epicentres of the virus, in an effort to contain it before it becomes too difficult a challenge to control,” he says.From China, Cambodia and Vietnam in the East, to North and South America in the West, H5N1 is spreading at a near-pandemic morbidity rate. Human infections have been reported in several countries but are so far limited to individuals in contact with birds. “International organizations are concerned that the virus might adapt to the human body, leading to human-to-human transmission. That would be catastrophic,” Al-Shishini says.