Analysis of Adaptation Mutants in the Hemagglutinin of the Influenza A(H1N1)pdm09 Virus

Abstract

Hemagglutinin is the major surface glycoprotein of influenza viruses. It participates in the initial steps of viral infection through receptor binding and membrane fusion events. The influenza pandemic of 2009 provided a unique scenario to study virus evolution. We performed molecular dynamics simulations with four hemagglutinin variants that appeared throughout the 2009 influenza A (H1N1) pandemic. We found that variant 1 (S143G, S185T) likely arose to avoid immune recognition. Variant 2 (A134T), and variant 3 (D222E, P297S) had an increased binding affinity for the receptor. Finally, variant 4 (E374K) altered hemagglutinin stability in the vicinity of the fusion peptide. Variants 1 and 4 have become increasingly predominant, while variants 2 and 3 declined as the pandemic progressed. Our results show some of the different strategies that the influenza virus uses to adapt to the human host and provide an example of how selective pressure drives antigenic drift in viral proteins.

The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability

“…This rapid and large change can give rise to new strains very different from any virus encountered previously, with the potential to cause a pandemic. 8 …”

“…These findings reveal some of the pathways that this pandemic strain used to disseminate in the human population as a response to selective pressure, such as receptor recognition, increased infectivity, and evasion of the immune response. 8 …”

Structural Stability of Influenza A(H1N1)pdm09 Virus Hemagglutinins

“…However, during this time a number of hemagglutinin (HA) mutations have emerged at sites that are within or close to the trimer's monomer-monomer interface (5). This raises the possibility that this reduced HA trimer stability might have been detrimental to the fitness of the virus in the human host and these recent mutations are being maintained within the HA to improve its stability.…”

Ethical Alternatives to Experiments with Novel Potential Pandemic Pathogens

“…Analysis of adaptive changes in HA of H1N1pdm [74], lipid tail protrusion as a determinant of HA-membrane fusion [75], and identifying determinants of inhibitorresistant NA [76] Biophysical basis for complex phenotypes…”