Mutated Protein Allows Flu’s Lethality in Some Patients

The flu can be lethal in some patients, but benign in others. The reason that this is the way that flu infections work might be the cause of a protein, which might be mutated in patients who are more easily affected by the flu than others.

The new study was published in the journal Nature, and lead researcher Paul Kellam, of the Sanger Institute in Cambridge, UK, bred mice with a mutation which stopped them from making the protein IFITM3. This protein is usually made by cells in response to a specific interferon, which is basically an immune signaling chemical that turns on body’s antiviral defenses.

Some strains of flu that did not sicken mice in the past, including the 2009 pandemic virus, now left mice without IFITM3 dying. The virus was able to penetrate deeper into their lungs, replicate at least 10 times more, and induce severe pneumonia.

People in ICUs with severe pandemic or seasonal flu in the UK were 17 times more likely than other Europeans to carry a non-functional gene for IFITM3. The team found that IFITM3 has become more common in the last 10,000 years, when humanity is supposed to have caught the first flu from livestock.

The protein affects viruses, which are normally taken inside the cell enclosed in a membrane bubble, including dengue and West Nile and the flu, by stopping them from reaching the cell nuclei. Instead, the viruses are routed to waste disposal sites. This finding suggests that a drug mimicking IFITM3 might be able to fight all of those viruses.

Reference: “IFITM3 restricts the morbidity and mortality associated with influenza” by Aaron R. Everitt, Simon Clare, Thomas Pertel, Sinu P. John, Rachael S. Wash, Sarah E. Smith, Christopher R. Chin, Eric M. Feeley, Jennifer S. Sims, David J. Adams, Helen M. Wise, Leanne Kane, David Goulding, Paul Digard, Verneri Anttila, J. Kenneth Baillie, Tim S. Walsh, David A. Hume, Aarno Palotie, Yali Xue, Vincenza Colonna, Chris Tyler-Smith, Jake Dunning, Stephen B. Gordon, The GenISIS Investigators, The MOSAIC Investigators, Rosalind L. Smyth, Peter J. Openshaw, Gordon Dougan, Abraham L. Brass and Paul Kellam, 25 March 2012, Nature.
DOI: 10.1038/nature10921

Dengue FeverDiseaseEpidemiologyFluIFITM3InfectionMutantMutationPandemicProteinWest Nile