Emergence and Convergence of H5N1 M230I in Egypt
Recombinomics Commentary
February 19, 2007
Recent NAMRU-3 generated sequences from H5N1 isolates from patients and poultry in Egypt, provide additional examples of the emergence and convergence of M230I. M230I was first reported in the first confirmed human case this season, in Gharbiya in October. The same change was found in the two sequences from the Gharbiya cluster. The similarity between the HA, NA, MP, and NS sequences from the two family members strongly indicate that the third family member was also fatally infected with H5N1 containing M230I.
The sequences coding for M230I in the above patients was also found in poultry in Egypt. These sequences are also in recent H5N1 sequences in China. However, M230I in poultry was also found in isolates with sequences that matched H7N3 in England as well as two H5N1 in Asia, A/duckGuangdong/173/04 and A/Ck/Hong Kong/2133.1/2003. This coding for M230I has now also been detected in a poultry isolate from this month as well as the most recent H5N1 patient (37F) from Fayyoum.
Thus, both versions of M230I have been identified in NAMRU-3 generated poultry and human sequences in Egypt. M230I is in most isolates, extending from the first reported sequence from this season, to the most recent human sequence. These sequences contain polymorphisms found in Qinghai H5N1 isolates and also have the regional markers that were present in the isolates from Egypt last season.
However, overlaid on this genetic background from last season are “new” polymorphisms, which include M230I, which is in the majority of the human and bird isolates tested to date. The acquisition of the new polymorphisms also appears to be via recombination, because sets of polymorphisms on multiple gene segments can be found in recent H5N1 isolates in China and the exchange pf genetic information between Qinghai H5N1 and the distinct, non-Qinghai H5N1 in Asia has been described repeatedly. These combinations include HA V223I and NA M31I in the Gharbiya cluster and Shantou geese isolates or the HA M230I in the recent sequence from Fayyoum as well as the NA polymorphism G707C which are present in the two H5N1 isolates listed above.
The widespread detection of M230I in Egypt is cause for concern. M230I is in the three major seasonal flu strains, H1N1, H3N2, and influenza B, which are efficiently transmitted human-to-human. Moreover, M230I is also in H7 isolates, which have also been shown to efficiently transmit human-to-human. M230I is also in H3N8 which has been found in horses and is efficiently transmitted dog-to-dog. Moreover, all cases in Egypt with reported M230I have died.
The detection of M230I in the majority of human or bird sequences raises concerns that M230I is becoming fixed in Egypt. M230I has not been previously reported in the Qinghai strain of H5N1, which has another human polymorphism, PB2 E627K, which has become fixed in the Qinghai strain.
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