Q226L mutation enables human receptor binding in H5 2.3.4.4e virus
Influenza A viruses (IAVs), particularly H5Nx strains, pose significant threats to both avian and mammalian species, with occasional spillovers resulting in human infections. A crucial barrier to sustained human-to-human transmission of H5Nx viruses is their limited ability to efficiently bind human-type receptors, a function primarily governed by the hemagglutinin (HA) protein.
New research published in PNAS investigates the potential of H5Nx viruses to adapt to human hosts by altering their receptor-binding properties, with a focus on the implications of the Q226L mutation within the HA protein. The study demonstrates that the Q226L mutation in the HA of the 2.3.4.4e strain of H5Nx influenza virus (The 2.3.4.4e strain of H5Nx virus studied in the article was isolated from a black swan in Akita, Japan) enables efficient binding to human-type receptors - a key requirement for viral transmission among humans. In contrast, the 2.3.4.4b strain requires additional mutations in its HA protein to achieve similar adaptation.
Using techniques such as glycan arrays and structural analyses, the authors elucidate how specific amino acid substitutions affect receptor-binding preferences, highlighting the pivotal role of the Q226L mutation in the 2.3.4.4e strain.
Understanding the molecular determinants of receptor specificity is essential for assessing the zoonotic potential of these viruses and for informing public health preparedness strategies against potential outbreaks.
