April 28, 2009

The Structure Of A Giant Virus

The mimivirus is the largest virus known to scientists, about half of a micrometer (0.0005 millimeter) in diameter. It is more than 10 times larger than the virus that causes the common cold and "“ unlike other viruses "“ is large enough to be seen with a light microscope. In this week's issue of PLoS Biology, an international team of researchers have determined key structural features of the mimivirus, findings that could help scientists study how the simplest life forms evolved and whether this unusual virus causes any human diseases.

Mimivirus infects amoebas, but it is also thought that it may act as a human pathogen, because antibodies to the virus have been discovered in people with pneumonia. However, many details about the virus remain unknown, said Michael Rossmann, Purdue University's Hanley Distinguished Professor of Biological Sciences.

Now, Rossmann and a team of researchers from Purdue, the University of California at Irvine, and the University of the Mediterranean in Marseilles, France, have determined the basic design of the virus's outer shell, or capsid, and also of the hundreds of smaller units - called capsomeres - making up this outer shell. Their findings confirmed the existence of a starfish-shaped structure that covers a 'special vertex' - an opening in the capsid where the genetic material leaves the virus to infect its host; an indentation in the virus's genetic material itself is positioned opposite this opening.

"The findings are important in terms of studying the evolution of cells, bacteria and viruses," said Siyang Sun, a postdoctoral research associate working in Rossmann's lab. "The mimivirus is like an intermediate between a cell and a virus. We usually think of cells as being alive and a virus is thought of as being non-living because it needs a host cell to complete its life cycle. The mimivirus straddles a middle ground between viruses and living cells, perhaps redefining what a virus is."

Researchers had previously been unable to determine the virus's structure because they had assumed that, like many other viruses, it's capsid had a design known as icosahedral symmetry. The paper's lead author, Chuan Xiao, discovered the true structure when he decided to try reconstructing the virus, assuming it had not the standard icosahedral symmetry but another configuration called five-fold symmetry.

"If you start out thinking the object has icosahedral symmetry, then you assume there are 60 identical pieces, and that influences how you reconstruct the virus's structure," Rossmann said.

The researchers took images of the virus using an atomic force microscope, revealing a pattern of holes regularly spaced throughout the virus's outer shell.

"The capsids of most other large, pseudo-icosahedral viruses do not contain such holes, and their function is unknown," Rossmann said.

The researchers used cryo-electron microscopy reconstruction to determine the structural details. This reconstruction method enabled them to reassemble three-dimensional images from two-dimensional pictures, much as a complete architectural drawing of a house can be assembled with two-dimensional drawings of the sides, the roof and other elements. An icosahedron has a roughly spherical shape containing 20 triangular facets and 60 identical subunits. Like an icosahedron, the mimivirus capsid also has 20 facets.

However, unlike an icosohedron, five facets of the capsid are slightly different than the others and surround the special vertex. Icosohedra contain 12 similar vertices, whereas the mimivirus contains eleven such vertices, with the 12th being different than the others.

The research, which is funded by the National Institutes of Health, is ongoing, with future work intended to study additional properties of the virus, particularly the structure of the starfish-shaped feature and how it functions.

Funding - The work was supported by the Keck Foundation for the purchase of an FEI CM300 electron microscope and by NIH grant AI11219 to MGR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests statement "“ The authors declare that no competing interests exist.

Citation: Xiao C, Kuznetsov YG, Sun S, Hafenstein SL, Kostyuchenko VA, et al. (2009) Structural studies of the giant Mimivirus. PLoS Biol 7(4): e1000092.doi:10.1371/journal.pbio.1000092


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