Mimivirus is the largest virus known to scientists, about half of a micrometre (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. An international team of researchers have now determined key structural features of Mimivirus, findings that could help scientists study how the simplest life forms evolved and whether this unusual virus causes any human diseases. Mimivirus infects amoebae, 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. Now researchers 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. 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. Mimivirus straddles a middle ground between viruses and living cells, perhaps redefining what a virus is. Scientists 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. These authors discovered the true structure when they tried 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.
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. 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.
Structural studies of the giant Mimivirus. 2009 PLoS Biol 7(4): e1000092
Mimivirus is the largest known virus whose genome and physical size are comparable to some small bacteria, blurring the boundary between a virus and a cell. Structural studies of Mimivirus have been difficult because of its size and long surface fibers. Here we report the use of enzymatic digestions to remove the surface fibers of Mimivirus in order to expose the surface of the viral capsid. Cryo-electron microscopy (cryoEM) and atomic force microscopy were able to show that the 20 icosahedral faces of Mimivirus capsids have hexagonal arrays of depressions. Each depression is surrounded by six trimeric capsomers that are similar in structure to those in many other large, icosahedral doublestranded DNA viruses. Whereas in most viruses these capsomers are hexagonally close-packed with the same orientation in each face, in Mimivirus there are vacancies at the systematic depressions with neighboring capsomers differing in orientation by 608. The previously observed starfish-shaped feature is well-resolved and found to be on each virus particle and is associated with a special pentameric vertex. The arms of the starfish fit into the gaps between the five faces surrounding the unique vertex, acting as a seal. Furthermore, the enveloped nucleocapsid is accurately positioned and oriented within the capsid with a concave surface facing the unique vertex. Thus, the starfish-shaped feature and the organization of the nucleocapsid might regulate the delivery of the genome to the host. The structure of Mimivirus, as well as the various fiber components observed in the virus, suggests that the Mimivirus genome includes genes derived from both eukaryotic and prokaryotic organisms. The three-dimensional cryoEM reconstruction reported here is of a virus with a volume that is one order of magnitude larger than any previously reported molecular assembly studied at a resolution of equal to or better than 65 A°.
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Human adenoviruses (HAdV) are non-enveloped double-stranded DNA (dsDNA) viruses associated with acute infections. Although these infections are generally self-limiting, the re-emergence of certain HAdV types has also been linked to potentially fatal respiratory infections in both civilian and military populations. In addition to their disease associations, replication-defective or conditionally replicating HAdVs continue to be evaluated in ~25% of approved phase I to III clinical trials for vaccine and therapeutic gene transfer. However, the lack of accurate details of the virus structure limits the reengineering of HAdV vectors and prevents a better understanding of the virus life cycle. High-resolution HAdV structure determination presents a challenge because of the large size (910 Å average diameter, 150 megadalton) and complexity (pseudo-T = 25) of the virus.
