Ursula Höfle
Contracted Lecturer, member of the SaBio Group at the Institute for Game and Wildlife Research (IREC) (CSIC-UCLM-JCCM)
The study published by an established group dedicated to the investigation of zoonotic virus characteristics and host immune response reports the finding of a new gene that adds to the already known mechanisms involved in the so-called species barrier that prevents avian influenza A viruses from easily infecting humans. This extensive study based on solid evidence worked out in great detail adds a gene to the already known factors inhibiting the transmission of avian influenza A viruses to humans - BTN3A3 - and tells how evasion of inactivation by this gene has allowed some avian influenza viruses to acquire zoonotic potential and infect humans, especially in the H7N9 subtype that caused a wave of human infections in 2013.
The study is based on the search for genes stimulated by interferon (the substance secreted as an immune response in our body) and combines cell culture studies, animal experiments and in-depth studies of human and primate genomes and avian influenza A viruses. Through the experiments, the researchers identified the BT3A3 gene as a specific inhibitor of avian influenza viruses both in cell culture and in a live mouse model. They also detected that the gene acts at the level of virus replication in the cell nucleus and the amino acid in the sequence of one of the segments of avian [influenza A virus] AIVs that makes avian influenza viruses susceptible to the gene's effect.
Finally, they describe two amino acid changes that can make avian influenza A viruses resistant to the gene, one of which is present in most avian influenza viruses that have, at some point in history, made the jump to humans - including the 1918 influenza virus (the misnamed Spanish flu). They conclude that these changes - that is, evasion of the species-hopping barrier constituted by the BTN3A3 gene - are a key mechanism that may confer zoonotic potential to avian influenza A viruses.