2023-04-18 17:05:04
Avian flu still circulates among birds, thus exposing people who have close contact with them to accidental contamination. The genome of the strain that infected a 53-year-old Chilean has been dissected by scientists. What does it reveal?
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On March 29, 2023, the Chilean Ministry of Health announced a case of H5N1 avian flu on its territory, the second in South America following that of a 9-year-old child in Ecuador. Today the National Influenza Centre of Chile publishes the results of genetic analyzes carried out on the strain that infected the 53-year-old man last March. This strain belongs to clade 2.3.4.4b, the same one that circulates all over the world and kills many birds, but it has new mutations involved in the ability of the virus to replicate in mammalian cells.
Mutations that betray an adaptation to mammals?
Virus RNA was collected following bronchopulmonary lavage performed on the infected patient who was hospitalized with severe pneumonia. Hemagglutinin is a protein located on the surface of influenza viruses that allows virions to enter the cells to be infected. By comparing the genetic sequence of the hemagglutinin taken from the patient with the other H5N1 viruses, the scientists noted only three mutations that do not modify the biology of the virus. These do not allow it to better infect mammalian cells. Neuraminidase is the second surface protein of influenza viruses which allows the release of newly formed virions. Here, no notable difference with the H5N1 strains circulating in birds in Chile.
The scientists also looked at the genes of the replication complex, the set of enzymes that allow the avian influenza virus to replicate its genetic material, including the PB2 protein or polymerase basic protein 2. There are two differences between the PB2 isolated from the Chilean patient and that isolated from the birds.
The first mutation is an amino acid substitution that might be a mammalian adaptation since it enhances the activity of RNA polymerase – the viral enzyme that helps replicate RNA genomes – in mammalian cells. A second, rarer substitution increases the efficiency of avian influenza virus replication in mammalian cells.
A virus on the way to becoming zoonotic?
The CDC notes in its report that the combination of these two mutations has already been observed in zoonotic strains of H7N9 avian influenza. However, it appears that these two mutations are not common in sick birds in Chile, suggesting, according to the CDC, that they arose once the virion had infected the 53-year-old man and his disease was progressing. Indeed, viruses can accumulate mutations when they replicate following infecting a host, this is a common phenomenon, especially when the infection is long or intense. These mutations are not sufficient to qualify H5N1 as a zoonotic virus and do not give it the ability to infect mammals or to be transmitted between humans. H5N1 remains under close surveillance.
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