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Nabel and colleagues took a closer look
at the HA protein. A discrete region of the HA's tip that plays a
critical role in binding to cells, they found, has a 95% similarity in
amino acid sequence between the old and new pandemic strains.
Comparisons between seasonal and the pandemic strains in this region
found less than 70% similarity.
In the second study, a team led by structural biologist Ian Wilson of the Scripps Research Institute in San Diego, California, went further, linking the amino acid sequence analysis to the three-dimensional structure. Wilson's group crystallized the 1918 and 2009 pandemic viruses and showed that the HA heads had distinctly similar shapes. "The closest related structure that we have to the current 2009 swine flu is the 1918 structure," says Wilson.
The above comments are from two papers published this week showing similarities between HA from 1918 and 2009 pandemic strains. One paper focuses on antigenic similarities and notes the high degree of identity in the receptor binding domain. The other paper notes similarities in structure. However, earlier structural studies noted similarities between 1918 and H5N1, which is avian, so similarities with 2009, which is swine is not a surprise, since 1918 is a human/ swine H1N1 recombinant. Similarly, antigenic similarities would be expected because the HA in the 2009 pandemic strain is from North American swine, which would be similar to the classical swine H1N1, including the first influenza isolate, from a pig in Iowa in 1930. Moreover, recent studies showed that survivors of 1918 had antibodies which recognized the 20009 H1N1 and anti-sera against 1918 offered better protection form a pandemic 2009 mouse challenge than anti-sera against the 2009 pandemic strain.
However, the two recent studies reinforce concerns about a serious pandemic evolving from the 2009 strain. Frequencies of D225G, as well as Tamiflu resistant H274Y are on the rise, and a new wave could have markedly higher levels of both components, leading to more severe and lethal cases. The current pandemic H1N1 is far more lethal to those under 65 than seasonal flu, and overall deaths have been reduced because of existing neutralizing antibodies in elderly populations due to exposure to the 1918 pandemic H1N1 or seasonal H1N1 circulating prior to 1950.
Although the number of deaths of the elderly is markedly reduced because of immunity to earlier versions of H1N1 and the absence of seasonal flu, today’s CDC report (week 12) indicates the P&I death rate is above the epidemic threshold, raising concerns that a large number of H1N1 deaths are not being reflected in state influenza reports or weekly updates. Recent reports have highlighted false negatives when samples from the upper respiratory tract are tested, leading to a large number of unrecorded deaths. Similarly the spike in hospitalizations in Georgia raises concerns that the frequency of D225G in fatal and severe cases is on the rise.
In 1918/1919, two of the five HA sequences had D225G, which is in the receptor binding domain, and as noted above, there is a 95% similarity between the 1918 receptor binding domain and the 2009 receptor binding domain. Moreover, the fatal cases linked to the 2009 virus has a mean age of 37.4, in marked contrast to ages for seasonal flu (75.7 years) or the two more recent pandemics in 1968 (62.2 years) or 1957 (64.6 years), but similar to the 1918 deaths (27.2 years).
The similarities between the H1N1 sequences from 1918 and 2009 continue to be cause for concern.