Tag Archives: mutation

Swine Flu: New and Improved!

Contributed by guest blogger: Marni Hershbain ’11

Flu season is never enjoyable, but some seasons are certainly worse than others. The 2009 swine flu outbreak was particularly serious because the 2009 H1N1 strain was a novel virus, formed via the reassortment of swine, avian and human flu viruses. There were over 600,000 confirmed cases of H1N1 and over 18,449 deaths during the course of the pandemic. While this sounds pretty bad, it could have been much worse. The transmission efficiency of H1N1 was actually much lower than those of other pandemic strains, such as the 1918 H1N1 strain. Unfortunately, recent research demonstrates that this could change.

Flu strains are characterized by the hemagglutinin and neuraminidase found on their surfaces, hence names like H1N1. In order for the virus to infect a cell, hemagglutinin on the surface of the virus must bind to glycan receptors on the cell. Therefore, to explain the low transmission efficiency of 2009 H1N1, researchers looked to its hemagglutinin.
In most flu strains, the amino acids at positions 219 and 227 within the hemagglutinin are both hydrophobic or both charged. In 1918 H1N1 both are hydrophobic. However, the 2009 H1N1 strain has isolucine, a hydrophobic molecule, in position 219 and glutamic acid, a charged molecule, in position 227. Researchers hypothesized that lacking either hydrophobic or ionic interactions at these positions would disrupt the positioning of neighboring residues and decrease the hemagglutinin’s binding affinity. They further hypothesized that if they replaced isolucine with the charged amino acid lysine, stable inter-residue interactions would occur and binding affinity would increase.

When researchers compared the ability of wild type and isolucine→lysine mutant strains to bind to an array of glycans representing human binding sites, they found the binding ability of the mutant strain was 30 times greater. The mutant version also bound more intensely to receptors in human tracheal tissue. Researchers also infected ferrets (commonly used as models in human influenza studies) with either wild type or mutant virus. Only the ferrets infected with mutant virus spread the infection to all of the previously uninfected ferrets placed in close proximity to them.

The mutation of just one amino acid could greatly impact the transmission efficiency of 2009 H1N1. Flu viruses tend to mutate frequently, which is why a new vaccine needs to be developed every year. Predicting what these mutations will be is not an easy task, but mutations at the positions in this study will certainly be monitored closely.