The H5N1 avian influenza virus continues to spread in the USA. It has infected poultry farms in 49 states, 718 dairy herds in 15 states, and caused 58 human cases. Worrying numbers, especially with regards to infections of cows and humans: the more the virus circulates outside its natural reservoir, i.e. birds, the greater chance it has of developing a mutation that makes it capable of effectively infecting our species, and to start spreading by human-to-human contagion. The consequences, in this scenario, could be serious. And unfortunately, this is not such a remote possibility: a new study in Science reveals that with a single mutation, the American H5N1 virus is able to adapt perfectly to the cellular receptors present in the upper airways of humans.
Special observation
H5N1 is a virus discovered in the mid-1990s. It infects birds, wild and farmed, without much distinction. And highly pathogenic strains are extremely lethal: in birds, but also in humans, at least according to the (few) confirmed cases of human infections, in which mortality seems to reach almost 30 percent. The real numbers are probably lower, because many asymptomatic or mild infections inevitably escape surveillance. But it is still a dangerous virus, which fortunately for now is not particularly good at infecting humans.
The membrane protein used by the virus to attach itself to the cells to be infected, hemagglutinin, is in fact adapted to hit its natural targets, birds. And therefore it recognizes with high specificity the “avian” receptors present on the cells of the respiratory tract of many birds. In our body these receptors are found in the deep respiratory tract (in the lungs, and this probably explains why the rare cases of infection have often proved to be serious) and in the conjunctivae of the eyes, which can act as a gateway to the virus while limiting its spread. systemic (and is probably the reason why human infections are often asymptomatic and escape the surveillance of health authorities). But they are not present in the upper airways, where influenza viruses normally affect.
The leap of species
The most feared possibility in recent weeks is that H5N1 develops a mutation that modifies the specificity for cellular receptors, making it suitable for infecting human receptors found in the nose, larynx and pharynx. By doing so, the virus could be able to easily infect humans, and spread through the population like a normal seasonal flu virus. And there would therefore be a real risk of epidemics, or even a pandemic.
A team of researchers from the Scripps Research Institute in La Jolla, California, decided to investigate how easy it is for the virus to adapt to human receptors. To do this, Californian scientists genetically modified viruses of the genotype taken from the first American patient infected with H5N1 during the current American epidemic, inserting a mutation suspected of having contributed to the species jump of other influenza viruses. By testing the virus thus obtained, they confirmed their fears: with a single mutation, which alters a single amino acid in the hemagglutinin chain, H5N1 acquires a high specificity for human cellular receptors.
The risks
The work was carried out in the laboratory, and only tested the effects of the mutation on the affinity of hemagglutinin for avian and human receptors. It is therefore not known whether the mutation alters the behavior of the virus in some other way, and therefore provides a real advantage compared to the genotypes currently circulating in the bovine population. Finding out will be the next step, which researchers from the Scripps Research Institute and other research centers will most likely work on in the weeks to come. While waiting for new results, the attention of the American health authorities should be directed to containing the circulation of the virus in cattle herds and in our species as much as possible: with each new infection in a mammal, H5N1 has one more opportunity to accumulate mutations and exchange genetic material with other human viruses, through a mechanism called reassortment, and thus transform into a virus perfectly adapted to attack our species.