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Human H5N1 in Anhui China Has HA Q226R

Recombinomics Commentary
April 3, 2006

China has release three H5N1 HA human sequences, A/Anhui/1/2005(H5N1), A/Anhui/2/2005(H5N1). A/Guangxi/1/2005(H5N1).  The isolates appear to be linked to the case of the pregnant woman from Anhui based on the title of the submissions.  WHO reports describe a 35F from Anhui (who developed symptoms November 11, 2005, was hospitalized on November 15, and died on November 25) as well as a 24F from Anhui who was hospitalized at about the same time, as well as a 10F from Guangxi who developed symptoms on November 23, 2005.

All three of these isolates were most closely related to an H5N1 isolate from Fujian province, A/duck/Fujian/1734/05(H5N1) and contain a number of distinctive polymorphisms including an HA cleavage site missing a lysine (RERRRKR), a glycosylation site due to A160T, changes near the receptor binding domain (P185S, R193K) and a change just upstream from the HA cleavage site at Q315L.  The notable changes as well as many more suggest that pandemic vaccines directed against the strain from Vietnam or Indonesia would have limited protection against the three isolates from China.

Moreover, A/Anhui/2/2005(H5N1) also has a change within the receptor binding domain due to A741G creating Q226R.  Donor sequences for this change are found in non-human H3 sequences, including swine.  Changes in the receptor binding domain are cause for concern and the changes could increase affinity for human receptors.

Earlier isolates from Hong Kong from two family members who had visited Fujian province had another change in the adjacent position in the receptor binding domain, S227N, which was associated with increased affinity for human receptors and was also found in the index case in Turkey.

The changes in H5N1 in human isolates in China clearly suggest the pandemic vaccine program may not be directed against a sufficient number of targets.  The change in the receptor binding domain also highlights the easy with which such changes can happen, which could significantly increase the efficiency of transmission to humans.

More sequences from human H5N1 cases in China would be useful.

The following isolates have donor sequences in HA for Q226R.

  DQ371929  A/Anhui/2/2005                            2005  H5N1
  DQ447186  A/swine/Taiwan/0408/2004        2004  H3N1   
  AY619977   A/Swine/Ontario/42729A/01       2001  H3N3   
  AY619969   A/Swine/Ontario/K01477/01       2001  H3N3   
  AY633172   A/mallard/Alberta/199/99            1999  H3N6   
  AY633372   A/pintail/Alberta/37/99                 1999  H3N8   
  L31949        A/Seal/Massachusetts/3911/92 1992  H3N3   
  L32024        A/Seal/Massachusetts/3984/92 1992  H3N3   
  CY006035   A/duck/New Zealand/38/1984    1984  H3N8   
  AJ252132   A/swine/Potsdam/35/82               1982  H3N2

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