Recombinant Human Qinghai H5N1 in Nigeria
Recombinomics Commentary
February 25, 2007
Recently the HA and NA sequences from H5N1, A/Nigeria/6e/07 from the first human case in Nigeria were released. As expected, the sequences indicated the isolate was the Qinghai strain (Clade 2.2) with expected polymorphisms in HA and NA, including the consensus HA cleavage site GERRRKKR.
However, the HA sequence had a number of regional specific markers indicating it was a recombinant which had acquired polymorphisms in the 2006 isolates in Africa in Europe. Two of the markers were found in isolates from Sudan and western Africa (Nigeria, Ivory Coast, and Burkino Faso) listed here and here. However, other polymorphisms were linked to Egypt and Djibouti, listed here and here. Yet another polymorphism was from Germany and Switzerland, listed here.
This recombining of regional specific markers onto a single gene sequence is easily explained by homologous recombination. Similar acquisitions are seen in the recent Qinghai H5N1 isolates from Egypt, which acquire polymorphisms found in recent isolates from China in Hunan and Shantou. These donor sequences however are on H5N1 isolates that are clearly not the Qinghai (Clade 2.2) isolates, and include a 3 BP deletion found in isolates from Hunan and Egypt.
This polymorphism tracing provides compelling evidence for recombination. Additional examples of such acquisitions are limited by the number of public sequences. Last season H5N1 was reported throughout Europe, the Middle East, and Africa. Many of these samples were sent to the WHO-affiliated lab in Weybridge. A report in May, 2005 indicated over 700 samples from Europe alone were H5N1 positive and a phylogenetic tree representing the HA sequences from approximately 80 of the isolate demonstrated the diversity in the isolates which were clearly the Qinghai strain that was introduced into the region from multiple sources, providing compelling evidence for transportation and transmission by wild birds. Most of those sequences were collected in March, 2006 or earlier, yet one year after collection the sequences are still being hoarded by Weybridge.
This year H5N1 is again being reported in teh region, with outbreaks in Hungary, England, Krasnodar, Moscow, Turkey, and Kuwait, with additional reports from Pakistan, Afghanistan, Egypt, Sudan, Nigeria, and Ivory Coast. Other than the human isolate from Nigeria, only isolates from Egypt have been released, by NAMRU-3 in Cairo.
The recombination of H5N1 in the human isolate in Nigeria is cause for concern. Additional fatal human cases in Nigeria gave inconsistent results, including the mother of the only confirmed case.
The sequences from last season should be released immediately, and additional sequences from the current outbreaks in western Africa, including Nigeria should also be released.
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Phylogenetic Trees