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Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades
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- Recombinomics, Inc
- US Navy Medical Research Unit 3 (NAMRU-3)
- Central Laboratory for Veterinary Quality Control, Giza
- Ministry of Health, Arabic Republic of Egypt
- NAMRU-3 Ghana Detachment
- Ghana Veterinary Services, Accra
- Noguchi Memorial Institute for Medical Research
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- Document Type:
- Manuscript
- Date:
- Received 10 September 2007 12:42 UTC; Posted 12 September 2007
- Subjects:
- Biotechnology, Chemistry, Evolutionary Biology and Ecology, Genetics, Immunology, 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. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. 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. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, 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. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany.
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8 comments on previous versionsThe full gene sequences of H5N1 from a mute swan in Krasnodar, A/Cygnus cygnus/Krasnodar/329/07(H5N1), are being released at Genbank. The isolate was collected on September 6, 2007, one day after A/chicken/Krasnodar/300/07(H5N1) was collected from a poultry outbreak. The chicken sequence has been described. It traces back to the massive wild bird outbreak at Uva Lake in Mongolia in the summer of 2006, and is closely related to recent sequences from England, Germany, France, Czech Republic, and Kuwait.
The swan sequence is virtually identical to the chicken sequence. Four gene segments (HA, NP, MP, and NS) are exact matches. PB1 and PA differ by one BP, while PB2 and NA each differ by two BP. Thus, the sequences are over 99.95% identical (6 differences in over 12,000 positions).
Like the chicken sequence, the swan sequence has NA G743A, the polymorphism that was appended onto multiple genetic clade 2.2 backgrounds in 2007, including the recently released sequences from Germany.
The sequence data again supports independent introductions of Qinghai (clade 2.2) sequences into Europe this year. The most recent sequences have all traced back to the wild bird outbreak at Uva Lake and suggest H5N1 has become endemic in Europe, with the Uva Lake strain becoming dominant.
Full sequences for H5N1 from twelve 2007 chicken isolates from Nigeria have just been released (listed below). Ten of the NA sequences are closely related to the human influenza NA sequence previously released (A/Nigeria/6/07). Like 2006 isolates from Nigeria, the human 2007 sequence did not have G743A. However, two of the four closely related sequences (A/chicken/Nigeria/1071-10/2007 and A/chicken/Nigeria/1071-22/2007) did have G743A. These sequences represent the eleventh H5N1 clade 2.2 genetic background that acquired G743A in 2007.
The initial Nature Precedings report describes six genetic backgrounds that appended G743A in early 2007. More recently, there have been multiple H5N1 outbreaks in Europe, including the recent outbreak in mute swans in England. As noted by DEFRA today, these sequences are closely related to recent sequences from Czech Republic and Poland. These comments indicate all reported H5N1 in Europe since the summer of 2007 have been related to the Uva Lake strain of clade 2.2.3.
The Uva Lake sequences did not have G743A, nor did the recent sequences from the outbreak in South Korea at they end of 2006. Those sequences were also closely related to the Uva Lake isolates. However, there have now been four NA sequences released from 2007 outbreak in Germany and Krasnodar, representing distinct Uva Lake clade 2.2.3 genetic backgrounds. All four have G743A.
The appending of the same synonymous polymorphism, G743A, onto eleven distinct clade 2.2 genetic backgrounds in Russia (Moscow and Krasnodar), Egypt (four genetic backgrounds), Ghana, Germany (Bavaria, Saxony, and Thuringen), and Nigeria, is not easily explained by selection of de novo copy errors.
These acquisitions are more consistent with a mechanism involving homologous recombination with a common donor sequence.
Most closely related to A/Nigeria/6/07
EU148414 A/chicken/Nigeria/1071-15/2007
EU148446 A/chicken/Nigeria/1071-30/2007
EU148406 A/chicken/Nigeria/1071-10/2007
EU148422 A/chicken/Nigeria/1071-22/2007Closely related to A/Nigeria/6/07
EU148358 A/chicken/Nigeria/1071-1/2007
EU148430 A/chicken/Nigeria/1071-23/2007
EU148438 A/chicken/Nigeria/1071-29/2007
EU148374 A/chicken/Nigeria/1071-4/2007
EU148382 A/chicken/Nigeria/1071-5/2007
EU148398 A/chicken/Nigeria/1071-9/2007Distantly related to A/Nigeria/6/07
EU148366 A/chicken/Nigeria/1071-3/2007
EU148390 A/chicken/Nigeria/1071-7/2007 - (Login to share with a colleague)
Additional information
- License:
- This document is licensed to the public under the Creative Commons Attribution 2.5 License
- How to cite this document:
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Niman, Henry, Saad, Magdi, Aly, Mona, Tjaden , Jeffery, Earhart, Kenneth, Monteville, Marshall, Mansour, Moustafa, El-Sayed , Nasr, Nayel, Ahmed, Abdelghani, Ahmed, Esmat, Hala, Labib, Emad, Ayoub, Ehab, Arafa , Abdelattar, 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.2007.459.3> (2007)
- Version info:
Henry Niman on 07 December 2007 17:16 UTC
Sequences from German wild birds infected with H5N1 over the summer have been released. One of the sequences, A/black-necked grebe/Germany/R1393/07, was from central Germany and was from one of the more than 300 grebes from the artificial lake at the border of Thuringia and Saxony-Anhalt. The other two sequences were from mute swans in central, A/Cygnus olor/Germany/R1359/07, and southern, A/Cygnus olor/Germany/R1349/07, Germany. All three sequences are closely related to the recent sequence from Krasnodar, A/chicken/krasnodar/300/07 (99.7%, 99.5%, and 99.4% identical). As expected, all four sequences map to the same branch on a phylogenetic tree.
The recnt DEFRA report gives similar numbers for the relationship between H5N1 in Suffolk, and the Czech Republic (99.8%) and Germany and France (99.3%). For multiple isolates in Kuwait and Germany, the identities with the Suffolk sequence were 99.4%-99.6% and 99.2%-99.4%, respectively. These numbers suggest all of these isolates trace back to the 2006 massive outbreak at Uva Lake in Mongolia in 2006, but each outbreak represents independent introductions by wild birds.
NA sequences from the German isolates were also released, and they were closely related to each other and the Krasnodar NA sequence. Like the Krasnodar sequence, all three of the German sequences had G743A, the polymorphism that was appended onto six different genetic backgrounds in Moscow, Egypt, and Ghana. All of these backgrounds were distinct from the German and Krasnodar sequences (and presumably the English, Czech, French, and Kuwaiti sequences, which likely also have G743A).
The earlier detection of G743A on multiple genetic backgrounds suggested that donor sequences were flying around Europe, the Middle East, and Africa undetected, and those donor sequences may have been the sequences identified in Europe and the Middle East in the summer/fall of this year.
Clearly the Uva Lake sequences have become widely detected in the past few months.