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Qinghai H5N1 Mutation PB2 E627K in All Human Flu Isolates

Recombinomics Commentary

July 9, 2005

>> To test virulence, mice and chickens were infected with the BhGoose/QH/1/05 (4) isolate. All eight infected chickens died within 20 hours and seven of eight infected mice died within 72 hours, and the last died 96 hours post-infection.Earlier isolates taken from ducks in China were less virulent in mice and chickens <<

The high virulence of Qingahi isolates in chickens and mice is cause for concern.  In laboratory experiments, high virulence in mice has correlated with the PB2 mutation E627K.  This mutation is very rare in birds.  Only two bird isolates at GenBank have E627K, A/Pheasant/Hong Kong/FY155/01-MB(H5N1), A/Ostrich/South Africa/9508103/95(H9N2), and only one is H5N1.  This isolate was from the brain of a mouse infected with virus that did not have this mutation.

However, E627K is found in all human isolates, regardless of sero-type and dating back to the first human isolate in 1933.  The acquisition of this human polymorphism does not bode well for humans infected with such an H5N1 virus. In 1997, E627K was detected in H5N1 in three patients.  Two died and one recovered from a critical condition. In 2003 there was one fatality in the H7N7 outbreak in the Netherlands, and the isolate, A/Netherlands/219/03(H7N7), from the fatal case had E627K.  The mutation has also been found from two patients in Thailand, A/Thailand/2(SP-33)/2004(H5N1) and A/Thailand/5(KK-494)/2004(H5N1).  Three patients in Vietnam, where the case fatality rate is high, also had isolates Vietnam A/Viet Nam/1194/2004(H5N1), A/Viet Nam/1203/2004 (H5N1), A/Viet Nam/3062/2004(H5N1) that had E627K.  The mutation was also found in most of the leopard or tiger isolates in Thailand (A/leopard/Suphanburi/Thailand/Leo-1/04(H5N1), A/tiger/Chonburi/Thailand/CU-T3/04(H5N1), A/tiger/Chonburi/Thailand/CU-T7/04(H5N1), A/tiger/Thailand/CU-T4/04(H5N1), A/tiger/Thailand/CU-T5/04(H5N1), A/tiger/Thailand/CU-T6/04(H5N1), A/tiger/Thailand/CU-T8/04(H5N1)), and most or all infected cats died.

Thus, it appears that acquisition of the human polymorphism, E627K by H5N1, increases virulence in mammalian hosts. 

The acquisition of mammalian polymorphisms is high in isolates in Vietnam and Thailand, as H5N1 continues to recombine and expand its host range and boxun reports indicate H5N1 is not taking prisoners.

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