EDITOR'S CHOICE IN MICROBIOLOGY
I. Marazzi et al., “Suppression of the antiviral response by an influenza histone mimic,” Nature, 483:428-33, 2012.
Flu viruses employ an arsenal of tactics to bypass the immune system, and now Ivan Marazzi and colleagues at the Laboratory of Immune Cell Epigenetics and Signaling at Rockefeller University have discovered a new trick: a protein of the H3N2 flu strain carries a sequence that looks like a human histone tail and accumulates in the nuclei of infected cells, where it interferes with the transcription of antiviral genes.
The configuration of a portion of the viral protein NS1 in the human H3N2 strain looks similar enough to a region on the human histone protein that it can regulate the assembly of chromatin complexes. Crucially, the histone mimic targets antiviral host genes, and binds and impairs a protein that plays a key role in regulating transcription elongation.
“It’s been long established that viral mimicry can occur,” said cancer researcher Joe Mymryk of the University of Western Ontario, who was not involved in the study and has recently found other evidence of epigenetic manipulation by viruses. “But when you find one like this that’s just so basic and so critical, I think it’s an exciting development.”
By mediating our response to the flu virus, Marazzi thinks the histone-mimic proteins may be beneficial—to both human and virus. Because this mediation of the body’s response balances viral virulence with host survival, H3N2 has persisted for more than 30 years. “It looks like the sequence has been maintained through positive selection,” said Marazzi.