NEJM -- The Genetic Archaeology of Influenza

Posted by Clark Venable on 12/9/2004

NEJM -- The Genetic Archaeology of Influenza:

" "Different strains of influenzavirus have different pathologic effects. For example, infection by the so-called Spanish influenzavirus caused more than 20 million deaths in 1918 and 1919, many of which were due to hemorrhagic pneumonia. To identify the critical components of this virus, mouse-adapted influenza A viruses (Panel A) were modified by Kobasa et al. so that these viruses expressed the form of hemagglutinin encoded by the gene of the 1918 Spanish influenza strain (HAsp), alone (Panel C) or in combination (Panel B) with the form of neuraminidase encoded by the gene of the 1918 Spanish influenza strain (NAsp). They concluded that the HAsp protein is critical to the enhanced cytokine production, inflammation, and hemorrhagic pneumonia that characterized this virulent influenza." "

" "This new study has important clinical and epidemiologic implications. Assuming that the mouse model at least partially reflects the important factors in the virulence of influenza in humans, further dissection of the HAsp molecule is warranted to help identify the critical structural motifs that confer enhanced virulence. This can be accomplished by performing site-directed mutational analyses of the HAsp gene and investigating the effects of these mutations on infection in the mouse model. The identification of these motifs may provide a new epidemiologic tool for surveillance of circulating animal and human influenzaviruses that could be used to predict the emergence of a new, highly virulent pandemic strain. In addition, these detailed molecular studies could facilitate the identification of antigenic epitopes to include in vaccines in order to protect people against related pandemic strains." "

The above comments are in reference to a recent article in Nature titled Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. This is exciting and excellent work which opens the way for more fundamental basic science animal research as well as clinical studies.

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