During last year’s pandemic, the H1N1 Influenza A Virus made itself a bigger nuisance than a stadium full of vuvuzelas at a World Cup match, and so the rush began to figure out how to stop it in its tracks. In a new Journal of Virology paper, investigators have discovered that a handful of cellular miRNAs are doing their part to slow the spread of H1N1 one cell at a time.
A crack research team from the Chinese Academy of Sciences and Sun Yat-sen University found that miR-323, miR-491 and miR-654 inhibit the ability of H1N1 to replicate in infected cells by creating a sort of cellular militia, leaving their normal activities behind to help fend off infection during times of crisis.
The Chinese scientists first used reporter assays to screen for miRNAs that targeted the H1N1 genome, and then checked those miRNAs for effects on its viral replication. Here’s some more of what they found once they studied things more closely:
- miR-323, miR-491 and miR-654 all target the same H1N1 gene, pb1, which is involved in transcription and replication of the viral genome.
- The three miRNAs all use the same pb1 binding sites, located in the 3’ coding region.
- Those pb1 miRNA binding sites are highly conserved in various influenza strains.
- miRNAs downregulate pb1 through mRNA degradation, not translational inhibition.
- miR-323, miR-491 and miR-654 were able to inhibit H1N1 replication endogenously, not just through expression vectors.
miRNAs have been shown to interact with viral invaders before (like miR-122 and HCV, or miR-29a regulating HIV latency) but this is the first report to show endogenous miRNAs acting as an anti-viral defense. I guess that’s one more thing you can put on the list of non-coding RNA roles. Go read up on all the infectious details at Journal of Virology, June 2010.