MRC National Institute for Medical Research, London
Science for Health
Flu virus in 3-D
04 June 2010
Influenza A virus is unique in its capacity to vary and this helps to make it a significant cause of human disease. Different strains arise through seasonal variation and pandemic infection can occur when new influenza viruses are introduced into the human population or after viral reassortment.
The virus genome contains eight separate RNA segments that encode eight structural proteins and four additional proteins. High resolution x-ray crystal structures have provided a molecular understanding of the function of some of these proteins. 3D studies of ultrastructure can further identify the specific molecular interactions that govern virus self-assembly and ultrastructural changes that are essential to membrane fusion and virion disassembly during cell entry.
Peter Rosenthal (pictured) and colleagues Lesley Calder, Sebastian Wasilewski and John Berriman, in NIMR’s Division of Physical Biochemistry, have combined electron cryotomography and analysis of images of frozen-hydrated virions to determine the structural organization of filamentous influenza A virus. They rapidly freeze influenza virus and image it unstained at low temperatures by electron cryotomography, which uses ‘low dose’ methods to capture structural detail before the electron beam destroys the virus. The three-dimensional pictures show how all the components including the genome and glycoproteins such as the haemagglutinin and neuraminidase (the target of Tamiflu) are arranged.
The matrix layer adjacent to the membrane is an ordered helix of the M1 protein and its close interaction with the surrounding envelope determines the morphology of the virion. The ribonucleoprotein particles (RNPs) that package the genome segments form a tapered assembly at one end of the virus interior. The neuraminidase, which is present in smaller numbers than the haemagglutinin, clusters in patches that are typically present at the end of the virion opposite to RNP attachment. These new images provide an understanding of how the virus assembles itself, and may suggest new targets for drugs. The virus strains studied, though not the pandemic swine flu strain, were those that would give the best chance of observing and understanding the filamentous structure typical of clinical virus isolates.
The study is a direct illustration of how basic science, combining new methods in biology, instrumentation, and computation, continues to bring new information about causes of disease. Similar methods provide new three-dimensional views of cells important to understanding a variety of diseases.
Peter Rosenthal
Tomogram sections of influenza A virus
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Tomogram sections of frozen-hydrated influenza A virus.
Slice through a flu tomogram
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Original article
The research findings are published in full in:
Lesley J. Calder, Sebastian Wasilewski, John A. Berriman, and Peter B. Rosenthal. (2010)
Structural organization of a filamentous influenza A virus.
Proceedings of the National Academy of Sciences, USA, epub ahead of print. Publisher abstract
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