Note: I’m still blogging from the beach, and with a slow wireless connection and using a smaller than normal netbook keyboard, so I’m keeping my blog entries relatively brief this week.
# 4786
An absolutely fascinating study this morning that reveals a previously unknown way for influenza viruses to adapt to, and replicate efficiently in, humans.
This not only helps explain the transmission of the 2009 H1N1 pandemic strain, it illuminates another way that other avian flu viruses (including H5N1) could someday become a `humanized’.
A little background is in order, then the study.
Scientists have long come to expect to find a couple of specific amino acids at two locations in an influenza virus’s polymerase PB2 protein that enable it to replicate efficiently in humans; Lysine at position 627 or asparagine at position 701.
The 2009 pandemic virus lacked both of these changes, yet replicated extremely well, breaking the `rules’ and greatly puzzling scientists.
Researchers have now discovered that Lysine at position 591 of the PB2 protein compensates for the lack of these other two changes.
Moreover, they also found by making this change to H5N1, the virus replicated efficiently in mammals and increased in virulence in mice.
The study, published in PLoS Pathogens is titled:
Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus
Yamada S, Hatta M, Staker BL, Watanabe S, Imai M, et al. 2010 Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus. PLoS Pathog 6(8): e1001034. doi:10.1371/journal.ppat.1001034
ABSTRACT
Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals.
However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals.
Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins.
These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals.
This is a long, complex, but ultimately fascinating research article, and many of my readers will probably want to read it in its entirety.
You’ll find additional mainstream media coverage on this story in Medical News Today and in this Reuters report.
This study not only helps to explain how novel H1N1 moved efficiently into the human population, it also highlights a new region of avian flu viruses that need to be monitored for changes that might signify an emerging threat to humans.
