A Computational-Experimental Approach Identifies Mutations That Enhance Surface Expression of an Oseltamivir-Resistant Influenza Neuraminidase
2011

Identifying Mutations That Help Influenza Resist Tamiflu

publication Evidence: moderate

Author Information

Author(s): Jesse D. Bloom, Jagannath S. Nayak, David Baltimore

Primary Institution: California Institute of Technology

Hypothesis

Can we predict secondary mutations that counteract the decreased neuraminidase surface expression caused by the H274Y oseltamivir resistance mutation in pandemic H1N1?

Conclusion

The study identified several secondary mutations that can enhance neuraminidase surface expression and potentially counteract the effects of the H274Y mutation in pandemic H1N1.

Supporting Evidence

  • The H274Y mutation decreases neuraminidase surface expression and activity.
  • Secondary mutations can restore neuraminidase activity to wildtype levels.
  • The PIPS computational approach was effective in predicting beneficial mutations.

Takeaway

Scientists found ways to help a virus that resists a medicine called Tamiflu by looking for special changes in its genes that make it work better.

Methodology

The study used computational approaches to predict secondary mutations and experimentally screened these mutations for their effects on neuraminidase activity.

Limitations

The predictions are based on computational models and may not account for all possible mutations; only a limited number of mutations were experimentally tested.

Digital Object Identifier (DOI)

10.1371/journal.pone.0022201

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