Cryo EM Microscope Captures First Images of HIV Virus in 3D 'Tomograms'

January 12, 2006

Brussels, 11 Jan 2006

Although it is the subject of intense research, no clear picture of what the HIV virus actually looks like was available until now. Research led by Professor Stephen Fuller from the Wellcome Trust Centre for Human Genetics in Oxford, UK, together with team members based in Munich and Heidelberg in Germany, has managed to uncover startling images of the virus.

Until now, images of the virus have been taken using either an electron microscope or X-rays to 'see' the virus, which is far too small to perceive with optical equipment. These images tend to be blurred and indistinct. Images taken with the X-ray Cryo electron microscopy technique (Cryo-EM) have given a better picture. But, with the virus varying in size from as little as 100 to as much as 350 nm at different stages in its life-cycle, building-up a picture has proved extremely difficult.

The team led by Professor Fuller has managed to use the Cryo-EM technique on inactive forms of the virus at a resolution of 2nm - two thousandths of a millionth of a metre. The team followed the virus as it went through the infectious stages, as the viruses were all then the same size. Bathed in a supercooled liquid, the candidate viruses had their images taken again and again and at different angles.

Computers combined hundreds of images to build a three-dimensional representation of the virus. The results are referred to as 'tomograms', enabling the team to examine the virus in 3D and make computer slices through the virus.

'We now have determined three-dimensional structures for around 70 HIV virus particles,' said Professor Fuller. 'The result, the first tomograms of authentic HIV, teaches us how a variable structure assembles to produce an infectious agent.'

The startling images show a central body which houses the genetic RNA and proteins. This body is not symmetrical, an oddity for viruses and so far a mystery. The process of infection reveals that the viruses are manufactured inside the infected cell, where they produce spoke-like 'Gag' proteins. These proteins steal tiny bits of the cells' own membrane for the new virus, providing a cloak.

Once the virus shell is complete, the Gag proteins then form the internal body housing the genetic material and the virus is now ready to leave and infect a new cell. Once the virus comes into contact with a new host, the central body opens to reveal the genetic material which infects the cell.

In the HIV virus, the cells targeted are the same cells typically used to fight disease - white blood cells. Researchers have found that white blood cells contain a chemical known as NF Kappa B, which the HIV virus needs to reproduce, making the body's first line of defence the ideal target for the HIV virus.

For further information, please contact: The Division of Structural Biology The Wellcome Trust Centre for Human Genetics Tel: +44 1865 287708

CORDIS RTD-NEWS/© European Communities, 2005
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