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More Efficient H5N1 Transmission in Aswan Egypt?
Recombinomics Commentary
March 26, 2007

It is a three-year-old girl who was tested positive to the deadly H5N1 bird flu virus, Egyptian Health Ministry spokesman Abdel-Rahman Shahin said.

The girl, identified as Hagar Mohamed Awadallah, came from southern Egyptian governorate of Aswan, about 700 km south of Cairo.

The above comments describe the third child (3F) from Aswan with confirmed H5N1.  The first child (10F) was hospitalized March 13.  The second child (2M) was hospitalized three days later, while the above child was hospitalized March 22.  Three cases hospitalized within a nine day period from the same region are cause for concern.  These patients appear to be infected with a milder strain of H5N1.

US NAMRU-3 has sequenced the HA and NA of the first two cases (
A/Egypt/2321-NAMRU3/2007 and A/Egypt/2331-NAMRU3/2007).  The NA from the two Aswan patients are identical, and closely related to isolates form two patients from central Egypt (Beni Suef A/Egypt/0636-NAMRU-3/2007 and Fayyoum, A/Egypt/1394-NAMRU3/2007.

The HA sequences in Aswan however, differ from each other by a single nucleotide, but are distinct from the patients in central Egypt, which have a 3 nucleotide deletion.  The 3 nucleotide deletion matches chicken sequences from Hunan province in China. In Aswan, the HA sequence has a novel cleavage site that matches earlier isolates from whooper swans in Mongolia.  Although the two sets of HA sequences match earlier HA sequences from China or Mongolia, all of the sequences from the Aswan patients have a series of polymorphisms that define isolates from Egypt.  Thus, the Aswan sequences have evidence supporting recombination and reassortment.

The acquisition of a new cleavage site in Aswan, is similar to changes in northern Vietnam in 2005.  In both cases the new HA cleavage site was associated with a lower fatality rate even though the new cleavage site was appended onto a highly virulent strain of H5N1.

Cleavage of HA is required for viral entry, and the polybasic cleavage site from H5N1 isolates initially identified in Asia, expands tissue tropism because the additional basic amino acids create new sequences targeted by tissue specific proteases.  Thus, different cleavage sites can produce different clinical presentations, as can changes in the receptor binding domain.

The novel cleavage site in the Aswan patients is the first reported patients with GERRRRKR.  All other reported human cases infected with Qinghai H5N1 had the consensus Qinghai sequence, GERRRKKR, which is closely related to the consensus sequence for Asia, RERRRKKR,

The sequence from the latest Aswan case is expected to have the novel cleavage site from Mongolia, and to be closely related to the two earlier cases, signaling a common source.

The sequences from the recent case will be of interest.

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