Friday, November 20, 2009

RBD225G present in all fatal ukraine cases at GISAID

Recombinomics | The patient data associated with the 10 Ukraine isolates sequenced by Mill Hill and deposited at GISAID has been updated with demographic information, suggesting that the samples were from 10 individuals and four of the samples were from deceased patients. These are the same four samples that have D225G (see list below). This association suggests that swine H1N1 with D225G is more aggressive and is cause for concern.

As noted earlier, D225G has been appended onto multiple genetic backgrounds via recombination, and the data from Ukraine adds further support. Samples from Ternopil and Khmelnitsky (see updated map) have a regional marker that is found in swine but no other human isolates. This marker is on all 6 Termopil isolates, indicating it was an early acquisition, but only the two fatal cases have D225G indicating it was appended onto the Ternopil genetic background. However, it is also found in the two fatal cases from Lviv, which do not have the regional marker. Similarly, earlier isolates with D225G represent distinct genetic backgrounds with D225G.

It was the jumping of D225G that allowed for prediction of the marker in Ukraine prior to release of the sequences by Mill Hill. This type of jumping has been described in detail for H5N1 and seasonal H1N1. This type of jumping via recombination and identification of markers that make frequent jumps are the underlying concepts that allow for the D225G prediction.

However, it is likely that D225G jumps will continue and the lethal marker will spread via Ukraine-like viruses, as well as virus that acquire D225G by recombination. Moreover, the absence of D225G in the nasal washes may signal mixtures of H1N1, with wild type dominating in the upper respiratory tract, and versions with D225G being expressed at highest levels in the lung, leading to false negatives in nasopharyngeal swabs, and cytokine storms in lung tissues where the aggressive virus with D225G is at high concentrations.