Reconstructing Influenza Pathogenicity

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Science  16 Mar 2001:
Vol. 291, Issue 5511, pp. 2051
DOI: 10.1126/science.291.5511.2051a

The 1918 pandemic of influenza A was extraordinarily virulent and killed tens of millions of people. The first genetic characterization of the 1918 virus from wax-embedded tissue samples showed it to be a novel H1N1 influenza A virus. In an effort to identify the basis for this virulence and to prepare for future epidemics, Basler et al. sequenced the H1N1 nonstructural segment (NS), which encodes NS1 and nuclear export protein. The NS1 protein is a type I interferon antagonist in the mouse and is responsible for immunosuppression during infection by influenza A.

Basler et al. regenerated influenza viruses from cloned DNA and, following stringent containment protocols, tested in mice the pathogenicity of NS1 derived from the 1918 strain. Unfortunately, their results are inconclusive, as their engineered virus containing the 1918 NS1 sequence did not behave more virulently in mice than control strains, quite probably because the 1918 virus is a human strain. Nevertheless, as Lederburg points out, this was no mean feat because sequencing the original, fragmented RNA remains arduous and virulence may well depend on a specific constellation of varying genetic elements. — CA

Proc. Natl. Acad. Sci.98, 2746 (2001); Proc. Natl. Acad. Sci.98, 2115 (2001).

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