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Mutations lead to increased pH1N1 replication, pot

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arirish View Drop Down
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    Posted: February 26 2016 at 6:27am
Study: Mutations lead to increased pH1N1 replication, potential virulence

Experimentally induced adaptations in the 2009 H1N1 influenza virus led to dramatically increased replication rates and decreased receptor-binding affinity in human lung cells, according to findings published this week in Virology.

A team of German and Austrian researchers serially passaged a 2009 H1N1 variant isolate in human A549 lung epithelial cells to determine factors that might affect the strain's future virulence.

After six passages, the virus's replication rate abruptly rose, causing a 100-fold increase in viral titers. Both the original isolate and the adapted strain infected A549 cells with similar effectiveness.

Investigators identified five mutations that occurred with a frequency of more than 20% in viral hemagglutinin (HA). Three of these mutations led to an amino acid change in viral proteins.

Two HA mutations, HA1 D130E and HA2 I91L, caused significant changes to the A549 receptor-binding affinity. The mutation HA1 D130E affects the HA globular head near the cell receptor binding site, while HA2 I91L is located on the HA stem.

HA1 D130E led to an eightfold reduction in cell receptor binding strength and was also responsible for increased viral titers in mice infected with the adapted strain.

The mutation HA1 D130 is significant for future surveillance efforts, as it was seen at a frequency of only 0.14% in H1N1 viruses in 2009 and 2010, yet has increased to a frequency of 2.8% in recent years, the authors note. They said that their study has importance for surveillance of changes in H1N1 virulence and vaccine development needed to respond to potentially high viral titers.
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