3-D images of a flu virus

Last week, The Lancet released a study stating that an influenza pandemic similar to the so-called Spanish flu pandemic that killed between 50 and 100 million people between 1918 and 1920 would kill about 62 million people today, with 96 percent of the deaths occurring in developing countries. It is reassuring to learn that researchers from the National Institutes of Health (NIH) have succeeded in imaging one of the viruses that causes influenza. This finding could help to discover how antibodies inactivate the virus -- and maybe save millions of lives.

Last week, The Lancet released a study stating that an influenza pandemic similar to the so-called Spanish flu pandemic that killed between 50 and 100 million people between 1918 and 1920 would kill about 62 million people today, with 96 percent of the deaths occurring in developing countries (details here, free registration required). It is reassuring to learn that researchers from the National Institutes of Health (NIH) have succeeded in imaging one of the viruses that causes influenza. So far, they've studied the H3N2 strain, but they could soon image other ones. This finding could help to discover how antibodies inactivate the virus -- and maybe save millions of lives.

This research effort has been done at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and led by Alasdair Steven, who manages the Laboratory of Structural Biology Research. Here is an excerpt from the NIH short news release.

A team of researchers led by NIAMS’ Alasdair Steven, Ph.D., working with a version of the seasonal H3N2 strain of influenza A virus, has been able to distinguish five different kinds of influenza virus particles in the same isolate (sample) and map the distribution of molecules in each of them.

Below is a picture showing the three-dimensional structure of this specific virus (Credit: NIAMS/NIH). "The viruses are about 120 nanometers -- about one ten thousandth of a millimeter -- in diameter. Here is a link to a better quality version.

The structure of the H3N2 flu virus

But how was this image taken?

The research team used electron tomography (ET) to make its discovery. ET is a novel, three-dimensional imaging method based on the same principle as the well-known clinical imaging technique called computerized axial tomography, but it is performed in an electron microscope on a microminiaturized scale.

This research work has been published by the Proceedings of the National Academy of Sciences under the title "Influenza virus pleiomorphy characterized by cryoelectron tomography" (Vol. 103, No. 50, Pages 19123-19127, December 12, 2006). Here is a link to the abstract and below is an excerpt.

Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging many identical particles.
In this study, we used cryoelectron tomography to visualize the 3D structures of 110 individual virions of the X-31 (H3N2) strain of influenza A. The tomograms distinguish two kinds of glycoprotein spikes [hemagglutinin (HA) and neuraminidase (NA)] in the viral envelope, resolve the matrix protein layer lining the envelope, and depict internal configurations of ribonucleoprotein (RNP) complexes.

This study is certainly extremely interesting. But we should remember that influenza pandemics can kill millions of people. This is why The Lancet released a study called "Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918–20 pandemic: a quantitative analysis" (Vol. 368, Issue 9554, 23 December 2006, Pages 2211-2218). And once you register for free on their site, you'll have access to the full text of this study (PDF format, 8 pages, 154 KB). It will tell you how your country could be affected by such a pandemic.

In "World Death Toll Of a Flu Pandemic Would Be 62 Million" (free registration required), the Washington Post gives an interesting insight: "The analysis, the first of its kind, found a nearly 40-fold difference in death rates between central India, the place with the highest recorded mortality, and Denmark, the country with the lowest. The reason for the huge variation is not known, but it may reflect differences in nutrition and crowding."

Sources: The National Institutes of Health (NIH) news release, December 29, 2006; The Lancet, December 23, 2006; and various websites

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