HIV, the virus which leads to AIDS and which affects 40 million people across the world, has been seen in 3D detail for the first time by Oxford scientists and their colleagues in Heidelberg and Munich.

The virus, which is around 60 times smaller than a red blood cell, is far too small for normal microscopes. Electron microscopes and X-rays can ‘see’ it, but often give unsatisfactory images because the virus varies so much in size and shape: one of the unique features of HIV is this size variation, which is in contrast to the uniformity of most viruses.

Professor Stephen Fuller from Oxford’s Wellcome Trust Centre for Human Genetics and his colleagues used a technique called cryo-electron tomography to look in detail at the morphology of the virus.

The technique has been used to see the virus before, but this painstaking attempt reveals the three-dimensional structure for the first time. The team took images of the individual viruses from hundreds of different angles. These images were then combined using a computer, giving an unprecedented three-dimensional view of the deadly agent, published in the journal Structure.

An HIV particle, like any virus, is not a cell but rather is strands of genetic code wrapped in protein. Viruses invade living cells and take them over by usurping the cell’s genetic code with the virus’s genetic code (which contains the instruction ‘replicate’).

HIV is a particularly successful virus, and the size and shape variability which makes it so hard to image is assumed to play a role in its success. A puzzling question was how HIV, unlike other viruses, managed to be so varied without losing its crucial structure. The new image of the particle gave new insights into that conundrum. Instead of the central region of the virus organising its growth, as in most viruses, the virus membrane and the core interact so that the core stops growing only when it reaches the membrane’s limit. The inner surface of the viral membrane ‘directs’ growth, which keeps the important parts of the structure consistent whilst allowing size variation.

‘This novel mechanism accommodates significant flexibility in lattice growth while ensuring the closure of cores of variable size and shape’, said Professor Fuller. ‘Identifying how the virus grows will allow us to address the formation of this important pathogen and understand how it accommodates its variability. This could inform the development of more effective therapeutic approaches.’

The microscopy was performed at the Wellcome Trust Centre for Human Genetics in Oxford and The Max Planck Institut f?chemie in Martinsried, and was supported by the Wellcome Trust.

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