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H5N1 Fujian Cleavage Site Evolution
November 6, 2006
But Chen Hualan, director of China's National Bird Flu Reference Laboratory, said they "lack scientific proof" and that her lab hasn't found one strain to be more prevalent than the others.
"The so-called 'Fujian-like virus' is not a new variant of the virus," Chen was quoted as saying by the China Daily newspaper.
"Gene sequence analysis of the virus shows that it shares high conformity with the H5N1 virus that was isolated in Hunan when bird flu broke out in early 2004," said Chen, whose lab does isolation and gene sequence analysis on samples from every domestic bird flu outbreak.
The above comments highlight differing views between researchers in mainland China and Hong Kong on the evolution and significance of the Fujian strain of H5N1 in China. Some of this disagreement may be related to the definition of the Fujian strain. The first H5N1 isolated if Asia was from a goose in Guangdong in 1996. It had an HA cleavage site of QRERRRKKR. Subsequently, various stains of H5N1 have emerged and they can be grouped by changes in the HA cleavage site, which are associated with additional changes throughout all eight gene segments.
Last weeks PNAS paper added 404 HA sequences to the database, which allows for easy tracing of the HA cleavage site. The Fujian strain has two changes. The first change involved the loss of one K, producing a cleavage site of QRERRRK_R. This cleavage site was first reported in late 2003 in a duck in Taiwan that was being smuggled from Fujian province, A/duck/China/E319-2/03, as well as a duck in Hunan, A/Dk/HN/5806/2003. Thus, as noted above, the missing K was detected in 2003. Moreover, the missing K can also be found in a 1998 H7N1 isolate from a peregrine Falcon in the United Arab Emirates, A/peregrine falcon/U.A.E./188/234/98. The list of H5N1 isolates with the missing K can be seen here. In addition to southern China, isolates in Indonesia in 2004 and Vietnam in 2005 were also found.
However, in the spring of 2005, a duck that had the missing K and the Q-->L change was also found. The list of isolates with both changes is found here. The motif with the two changes spread rapidly throughout southern China, and included wild bird isolates in Hong Kong as well as isolates from Laos and Malaysia. Moreover, all human isolates from China in 2005 and 2006 had this change as did additional 2006 human isolates described in a report by China's Ministry Of Health.
These Fujian isolates have regions of identity with the Qinghai strain and highlight the evolution of H5N1 via recombination. The HA cleavage site with just the dropped K was found in Indonesia H5N1 which was on an Indonesian genetic background, which was also seen in the 3' half of the cleavage site which was also detected on an H7 genetic background. Similarly, one of the Indonesian isolates also had a Qinghai cleavage site on an Indonesian background.
However, it is recombination in wild birds between Qinghai and Fujian sequences that is driving the emergence of the new strain in China. Fujian sequences have also been detected in a Qinghai isolate in Romania, further highlighting the evolution of H5N1 via recombination.