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H5N1 PB2 E627K in Japan Duck Meat Imported from Shandong
July 12, 2005
>> Although only one of our two mouse brain variants possessed the E-to-K mutation at position 627 in PB2, this was the only common amino acid substitution detected in the variants studied by Lipatov et al. (2003). This PB2 mutation is responsible for the high virulence of Hong Kong H5N1 virus in mice (Hatta et al., 2001). It was also detected in an H7N7 virus isolated from a lethal human case during an outbreak in the Netherlands in 2003 (Fouchier et al., 2004) and in H5N1 viruses isolated from patients who died from their infection in 2004 (Govorkova et al., 2005, Li et al., 2004 and Puthavathana et al., 2005). Notably, the PB2 lineage to which Dk/Yokohama/aq10/03 and the Netherlands H7N7 virus belong is different from that of the 1997 Hong Kong H5N1 viruses (see Fig. 1b), which may reflect the dominant nature of this mutation. Thus, while highly pathogenic avian viruses become lethal to mammalian species as a result of multiple different mutations, the E-to-K mutation in PB2 appears to be an important event in this process. <<
The above comments are in an upcoming Virology paper on H5N1 in duck meat imported by Japan from Shandong province in 2003. The isolated bird flu virus , A/duck/Yokahama/aq10/03, was from duck meat destined for human consumption and the H5N1 isolated was viable. It cause neurological problems in mice and two variants (MBV-1 and MBV-2) were isolated from mouse brain. Both had single nucleotide changes in the PB2 gene, 12 nucleotides apart (G1879A and A1891C). The change at G1879A is the same mutation in the various H5N1 and H7N7 isolates described previously, and matches the change found in all 8 Qinghai Lake isolates.
Since the duck meat H5N1 mutation was found only after passage through mice, it is like the only other mouse isolate. E627K was not found in the parental virus, but was detected only after passage through a mouse brain.
However, E627K is found in all human flu isolates and now is in all avian isolates from Qinghai Lake.
H5N1 continues to acquire human polymorphisms, which can be quite lethal in an H5N1 or H7N7 virus.