Protein-folding mechanism speeds up flu virus evolution

Massachusetts Institute of Technology findings could be used to outwit the flu virus and prevent it from developing resistance to antivirals and vaccines.

Flu vaccination being administered

Researchers have found that flu viruses’ rapid evolution relies in part on their ability to hijack some of the cellular machinery of the infected host cell.

The team, from the Massachusetts Institute of Technology (MIT), showed that a class of cellular proteins known as chaperones, which influence protein folding, can direct the flu virus towards developing certain types of mutations.

They say the findings could potentially be used to prevent the flu virus developing resistance to antivirals and vaccines through use of drugs targeting the chaperone proteins.

“It’s relatively easy to make a drug that kills a virus, or an antibody that stops a virus from propagating, but it’s very hard to make one that the virus doesn’t promptly escape from once you start using it,” said lead author Matthew Shoulders from MIT.

“Our data suggest that, at some point in the future, targeting host chaperones might restrict the ability of a virus to evolve and allow us to kill viruses before they become drug resistant.”

In the study, published in eLife, the researchers took mammalian cells with different levels of chaperone proteins and infected them with H3N2 influenza[1]
. The cells were then propagated for nearly 200 generations.

The researchers found that the levels of chaperone proteins influenced both the rate and type of mutations arising in the viral population. For example, the gene for the hemagglutinin protein, the primary target of flu vaccines, was more likely to develop mutations in cells with high levels of chaperones.

Mutations also arose more rapidly in cells with high levels of chaperones, which the researchers suggest means the flu virus will acquire traits that could allow it to evade therapeutics quicker than in cells with lower chaperone levels.

Shoulders and colleagues say the findings are important because chaperones vary across tissues and species, as well as disease states such as fever, meaning this could alter the avenues available for the flu virus to evolve. Previous research has shown that the flu virus interacts with chaperone proteins and hijacks them for its own purposes.

The researchers think that in future, therapeutics could be developed that target this system of proteins, to try and prevent treatment resistance evolving. Chaperone inhibitors are already being studied in clinical trials for cancer, they note.

The researchers now plan to study the impact of chaperone proteins on the development of treatment resistance in the lab, and have begun exploring the role of chaperones in HIV, another virus to which they think the findings could be relevant.


[1] Phillips AM, Gonzalez LO, Nekongo EE, et al. Host proteostasis modulates influenza evolution. Elife 2017;6:e28652. doi: 10.7554/eLife.28652.

Last updated
The Pharmaceutical Journal, Protein-folding mechanism speeds up flu virus evolution;Online:DOI:10.1211/PJ.2017.20203686

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