Avian flu jumping to humans is rare, study reveals – 07/18/2023 – Health

The evolutionary leap required for a strain of the avian flu virus to infect humans occurred a few times and was the result of years of adaptation, reveals a study published this Monday (17) in the specialized journal PNAS (Proceedings of the National Academy of Sciences).

According to the research, alterations in the hemagglutinin protein (HA, the letter “H” of the types of influenza), mainly responsible for binding the virus to host cells, occurred twice in the evolutionary history of influenza A H3N2, responsible for the avian flu pandemic in 1968 that started in Hong Kong.

From 1968 until 2009, when there was a new global avian flu pandemic, the virus did not evolve to more effectively infect humans or to adapt to our species, as happened with H1N1. Despite having presented an initial adaptation to receptors present in human cells, it began to present the generic form (which infects both birds and mammals, including humans) a few years later.

The affinity for human cells, therefore, is not the only factor that will indicate the ability of the virus to jump between species (called “spillover”), but also its rate of transmission —the more animals infected, the greater the risk—, its presence in different tissues – if it affects more the upper respiratory tract, with dissemination by coughing or sneezing, or lower, which transmits with closer contact – and other mutations that can facilitate the infection from human to human.

“The hemagglutinin mutation of the avian influenza virus for humans was not enough to lead to the natural selection process of this virus in our species, being a slow and step-by-step process in which several factors, including mutations in the nuclear genes of the virus , participate,” says Erik de Vries, a researcher at the Faculty of Veterinary Medicine at the University of Utrecht (Holland) and coordinator of the study.

The research thus encapsulates a view over many years of how the influenza A virus would have evolved rapidly and successively to become more “adapted” to humans. “To date, the avian flu epidemic affecting farmed and wild animals around the world has not established sustained human-to-human transmission, and our study has demonstrated that such events are rare,” he said.

The scientist recalls, however, that the current strain of H5N1 avian flu is considered highly pathogenic for the animals it infects. In the United States alone, more than 58 million birds have been culled due to infection with the virus.

Last Wednesday (12), the WHO (World Health Organization) issued a warning about the dangers of recurrent outbreaks of avian flu for human transmission. According to the agency, the infections have already caused huge losses in animal populations, both wild and farmed birds and mammals, affected the food production chain and caused damage to farmers and livestock.

Cases in mammals are of particular concern due to their proximity to humans, even raising suspicions of a possible “adaptation of the virus to infect humans”, in addition to being able to serve as “intermediate hosts for virus mutation”, writes the organ.

In Brazil, data from the Ministry of Health confirm 62 outbreaks of avian flu in seven states (Espírito Santo, Rio de Janeiro, Rio Grande do Sul, São Paulo, Bahia, Paraná and Santa Catarina) from May 15 to the last 11. There were also 417 people exposed to probable or confirmed birds, with zero cases in humans confirmed, 36 discarded and two still under investigation.

In the PNAS study, scientists analyzed strains of the H3N2 virus over more than 50 years to assess the pathogen’s affinity for receptors in birds and humans. Analysis at the molecular level (or what happens inside cells, including genes that are activated) made it possible to measure the evolution of the virus in terms of strength (if it manages to maintain itself for a long time) and specificity (if it only binds to receptors specific) of the connection.

From the 1968 strain, eight years passed until mutations that generate greater affinity with human receptor cells emerged: alterations to bind to human sialic acid (Sia) 2 and 6. Receptor-binding mutation in birds (Sia 2 and 3). The H5N1 strain only shows affinity for avian cells.

Then they tested whether low doses of the virus were enough to cause human cells to become infected, or whether high doses were necessary. The conclusion was that, for infection to occur, low doses of the virus with greater affinity to the recipient cells ensure binding, but not cell-to-cell transmission. “The mutation would not only have to occur, but also many copies of the virus [replicação] would have to be generated to ensure transmission to humans, and this is rare”, explains the researcher.

For Fernando Spilki, a virologist at Rede Corona-ómica BR linked to the MCTI (Ministry of Science, Technology and Innovation), the study materializes knowledge that many specialists have warned about viruses, which is precisely the importance of specific contagion conditions for the occurrence of “spillover”.

“It’s not just an adaptation [para humanos]it is necessary to have sufficient replication in different spheres of the respiratory tract where [o vírus] could be expelled in large quantities and, for the time being, this is not the case with H5N1”, he said.

However, the increasingly close contact with wild animals, mainly due to the advance of deforestation, which has pushed the animals closer to large urban centers, in addition to the large number of mammals and poultry affected in the world, raises concern.

“As we saw with Covid-19, a high contagion rate brings more risks of the virus replicating and mutating. That is why it is important to create monitoring, animal and epidemiological surveillance systems and to prepare, including with vaccine stocks adapted to the strain. Here, the Butantan Institute has this capability.”