Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades
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- Recombinomics, Inc.
- Central Laboratory for Veterinary Quality Control, Giza, Egypt
- Ministry of Health and Population, Arabic Republic of Egypt
- NAMRU-3 Ghana Detachment, Accra, Ghana
- Noguchi Memorial Institute for Medical Research, Accra, Ghana
- U.S. Naval Medical Research Center
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- Document Type:
- Manuscript
- Date:
- Received 07 May 2008 22:53 UTC; Posted 08 May 2008
- Subjects:
- Biotechnology, Ecology, Genetics & Genomics, Microbiology, Bioinformatics
- Abstract:
Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1,2. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 3. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 4-7. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 8. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, Kuwait, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. The recombination role is further supported by the high fidelity replication in swine influenza 9 and aggregation of single nucleotide polymorphisms in H5N1 clade 2.2 hemagglutinin 10.
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11 comments on previous versionsSequences from H5N1 Egyptian isolates collected during the 2006/2007 season were recently released at Genbank. Earlier, the HA sequences from these isolates demonstrated that five of the poultry isolates from Beni Suef had a 3 BP deletion, which matched the deletion in H5N1 from patients in Beni Suef and adjacent governorates, including Fayoum. Additional HA sequences from human isolates from the 2007/2008 season were also recently released, and two of the Fayoum isolates, A/Egypt/2289-NAMRU3/2008 and A/Egypt/2549-NAMRU3/2008 also had the 3 BP deletion, indicating the deletion was stable and present in Egypt for the past two seasons. This deletion was appended onto an Egyptian clade 2.2 background and the deletion matched H5N1 poultry from Hunan province in China. The presence of the same 3 BP deletion on two different genetic backgrounds supports acquisition via homologous recombination.
Two of the earlier Egyptian isolates with the 3 BP deletion also had G743A on the NA sequence. The acquisition of G743A also represents another recombination event because it was present on multiple genetic backgrounds in Egypt, and all of the acquisitions were in early 2007. Two of the NA sequences which were recently released, A/chicken/Egypt/R2/2007 and A/chicken/Egypt/R5/2007, also had G743A. Although these isolates also had the 3 BP deletion, they were phylogentically distinct from the human isolates described earlier. Thus, there are now four isolates with the 3 BP deletion, which map onto two separate branches, signally two independent events (see list below).
These two events are in additional to the other H5N1 isolates which represent 3 additional independent events. Thus, in Egypt there are 8 H5N1 isolates with G743A, representing 5 genetic backgrounds which acquired G743A in early 2007. These events, like the same acquisitions in Russia, Kuwait, Ghana, and Nigeria signal acquisition of the same single nucleotide polymorphism by homologous recombination.
G743A in Bold
3 BP Deletion Branch 1
A/Egypt/1394-NAMRU3/2007
A/Egypt/2621-NAMRU3/2007
A/Egypt/2629-NAMRU3/2007
A/chicken/Egypt/9400-NAMRU3/2007
A/Egypt/2289-NAMRU3/2008
A/Egypt/2546-NAMRU3/20083 BP Deletion Branch 2
A/Egypt/2631-NAMRU3/2007
A/chicken/Egypt/R2/2007
A/chicken/Egypt/R3/2007
A/goose/Egypt/R4/2007
A/duck/Egypt/R5/2007
A/chicken/Egypt/R6/2007HA and NA sequences from the H5N1 outbreak in Assam, India in November, 2008 have been released at Genbank (A/chicken/Assam/140187/2008 and A/chicken/Assam/140203/2008). The sequences are the Uvs Lake version of clade 2.2.3 which spread throughout Europe between the summer of 2007 and early 2008. All published NA sequences from those outbreaks had G743A. In contrast, the 2008 sequences from India do not.
However, G743A was not on the initial sequences which came from a massive wild bird outbreak at Uvs Lake in Mongolia (as well as adjacent areas in southern Russia) in the summer of 2006. The strain was subsequently associated with outbreaks in South Korea and Japan in late 2006 / early 2007. Those sequences also did not have G743A. It was acquired by Uvs Lake sequences that were associated with the poultry outbreak in Kuwait in early 2007. At the same time G743A was also acquired by multiple clade 2.2 backgrounds in Egypt, as well as distinct clade 2.2.3 isolates in Russia and clade 2.2 isolates in Ghana and Nigeria.
Thus, the absence of G743A in the Uvs Lake sequences in India suggests that birds carrying those sequences had not traveled west into Europe, the Middle East, and Africa, but remained in the South Asia flyway that connects India with Mongolia and southern Russia.
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- This document is licensed to the public under the Creative Commons Attribution 3.0 License
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Niman, Henry, Aly, Mona, Arafa, Abdel-Satar , El-Sayed, Nasr, Nayel, Ahmed , Abdelghani, Ahmed , Esmat, Hala , Raczniak, Gregory , Agyen-Frempong, Mensah , Ampofo, William , and Boynton, Bruce. Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.459.4> (2008)
- Version info:
Henry Niman on 11 May 2008 15:35 UTC
A new HA sequence is being released from Saudi Arabia, A/falcon/Saudi Arabia/6732-2/2007. It differs from the earlier sequence, A/houbara bustard/Saudi Arabia/6732-1/2007, at only one position (both are clade 2.2.3). However, that change is also found in human and bird isolates from central or upper Egypt (clade 2.2.1), which extends the number of 2007 Egyptian acquisitions that are also found in 2007 clade 2.2.3 isolates.
A/duck/Egypt/07322S-NLQP/2007
A/goose/Egypt/07364S-NLQP/2007
A/chicken/Egypt/07181-NLQP/2007
A/Egypt/4226-NAMRU3/2007
A/Egypt/4082-NAMRU3/2007
A/Egypt/4081-NAMRU3/2007
A/Egypt/2750-NAMRU3/2007
A/Egypt/2620-NAMRU3/2007
A/Egypt/2616-NAMRU3/2007
A/Egypt/2331-NAMRU3/2007
A/Egypt/2321-NAMRU3/2007