1918 again? – Part 2

Yesterday, I wrote about a study that made the surprising discovery that although vaccines against recent H1N1 and H3N2 viruses offered poor protection, a vaccine against the 1918 H1N1 virus was completely effective against pandemic 2009 H1N1.

Another study relating to the resemblance between 1918 virus and the 2009 pandemic H1N1 virus was recently published. This work examined the three dimensional structure of the hemagglutinin (HA) protein, the same protein that was featured in the paper I discussed yesterday.

Although sequences are frequently discussed in Flublogia, the importance of protein structure receives less attention. This is unfortunate because it is the three-dimensional structure of proteins that gives them their function, not their sequence per se. If you know the nuclei acid sequence for a gene, you can work out the amino acid sequence of the protein it codes for. However, this information is insufficient to determine what the protein actually looks like because once it is synthesised it folds up into a complicated three-dimensional structure. Predicting final form from sequence is termed the protein folding problem. Computer programs are getting better at solving this problem, but they still cannot be relied on with complete confidence. To be certain of a protein’s true shape, you must first get a large amount of it and crystallise it. A scientist, called a protein crystallographer, can then take a picture of the protein crystal with a machine that uses X-rays. Computers then use this information to create three-dimensional models of the proteins.

A paper from Ian Wilson’s laboratory at The Scripps Research Institute used protein crystallography to characterise certain parts of the HA protein in the 2009 pandemic H1N1 virus, seasonal flu viruses and the 1918 virus. Specifically, they examined the binding of an antibody isolated from a survivor of the 1918 pandemic (2D1) to the HA proteins of several viruses.

From the study:

The antibody-binding site for 2D1 is well conserved in SC1918 and CA04, but not seasonal HAs (table S3).

[SC1918 is a flu strain from the 1918 “Spanish” influenza while CA04 is a strain from the 2009 pandemic virus]

This work provides further support for the speculation, also advanced in the vaccine study, that people exposed to the 1918 virus have substantial protection against the 2009 pandemic virus, but that exposure to more recent flu viruses offer little or no protection. Both of these papers were foreshadowed by results from a previous paper from Yoshihiro Kawaoka’s laboratory. This group found that sera collected from many residents of nursing homes who were born before 1918 contained neutralising activity to  the 2009 pandemic H1N1 virus but people born after 1920 did not.

There is now substantial evidence that there is a significant similarity between the 1918 virus and the 2009 pandemic flu virus with important implications for vaccine development. The question remains, however, how and why did this similarity arise? This leads us to speculation, which will be the subject of my third blog on this subject.

References

Xu et al. (2010) Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus. Science.

Wei et al. (2010) Cross -Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design. Science Translational Medicine.

Itoh, et al. (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature.

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