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E627K Circulation in Pandemic H1N1 Patients in the Netherlands
Recombinomics Commentary 08:22
September 29, 2009

The 1st day of illness was on 9 Aug 2009, when the patient was vacationing on one of the West Frisian Islands in the wetlands north of The Netherlands (Waddenzee).

The girl was ill for a week, with full recovery after 2 weeks. Our 2nd case with a virus shedding carrying the PB2 mutation is the younger sister and became ill on Thu 23 Jul 2009.

The above comments describe two patients in the Netherlands who were inflected with swine H1N1 with PB2 E627K.  The time gap in disease onset dates suggests these two events were not directly linked and support widespread E627K in this location and sub-clade.  In July and August twenty-four cases were lab confirmed, but only tweve were sequenced, so it is unclear if the sister of the July case also had E627K.  Since 10/12 of the sequenced isolates were related,but E627K was only identified in 2 of the 10, it is likely that the circulating virus was a mixture which is efficiently transmitting E627K, and the two positive sequences represent selection of E627K.

Earlier, E627K was reported in a patient from Shanghai.  The original sample and the first sub-clone had E627K, while the second sub-clone did not, suggesting the E627K was unstable.  The presence of E627K in two of ten related isolates raises concerns that E627K is transmitting as  a minor population, which is becoming increasingly more prevalent. 

Since this polymorphism supports optimal growth at a lower temperature, this version of PB2 may become much more prevalent as the temperature drops, and may lead to higher levels of virus which could have catastrophic consequences.

The levels of H1N1 have increased dramatically in the northern hemisphere and the rise is associated with the start of a new school year.  In many areas, cases are reported to be more severe leading to deaths among previously healthy pediatric cases in middle schools and high schools.  The targeting of students and the increase in fatal cases may be linked to viral load, which cold increase dramatically in viruses with E627K when the temperature drops.

Moreover, mixtures of virus could lead to higher levels in the upper respiratory tract initially, which could lead to higher levels of E627 in the lower respiratory tract due to initial copying by E627K.  Thus, a mixed infection could produce high levels of two different viruses in the upper and lower respiratory tract.

Release of sequence data and serious cloning efforts and sequencing of original clinical samples would be useful.

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