RBD D225G in China and Australia Raise Ukraine Concerns
The recent outbreak in Ukraine has raised concern that receptor binding domain changes are responsible. Although WHO has issued a new Ukraine situation update and has addressed preliminary changes in a news conference, they have not rule out receptor binding domain changes, and the recent announcement of investigations by two WHO Regional Centers (NIMR in Mill Hill, UK and CDC in Atlanta GA) suggests single nucleotide changes are under investigation.
One such change is the receptor binding domain polymorphism D225G which is present on recently released sequences from China and Australia. The HA sequence from China, A/Zheijiang/DTID-ZJU03/2009, is virtually identical to two earlier sequences from Yiwu (A/Zhejiang/DTID-ZJU02/2009 and A/Zhejiang-Yiwu/11/2009) and all were collected in September and appear to be from the same patient or contacts. The patient eventually recovered, but was seriously ill and hospitalized for several weeks. However, the three sequences from Yiwu match (see list here) sequences from an isolate, A/Hangzhou/1/2009, that is in another location in Zheijiang (see map), indicating D225G was appended onto the Hangzhou genetic background via recombination.
A sequence released Monday at GISAID by the WHO regional center in Australia, A/Sydney/2503/2009, also has D225G, but on a different genetic backbone. The 5' end of the gene matches isolates from Singapore and Japan (see list), which do not have D225G. Thus, D225G is appended onto this background via recombination, but the background in Australia is distinct from the background in China.
Similarly, the two genetic backbones described above are distinct for two isolates in Sao Paulo, which were from fatal cases. The lung isolates signal the jumping of D225G from one genetic backbone to another. This concurrent acquisition has been described in H5N1, as well as the genetic hitchhiking of H274Y in seasonal H1N1.
This jumping of the same polymorphisms form one background to another signals major changes, especially when the polymorphism "in play" is a receptor binding domain change, which is cause for concern.
The recent activity in Ukraine raises concerns that similar changes are in play there, and the failure of WHO to release the sequences or comment on receptor binding domain changes significantly increases these concerns.