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How viruses can drive a cell to suicide

DNA can spell danger, and may even drive a cell to suicide, according to new research from Queensland scientists.

A team led by Dr Kate Stacey from the Institute for Molecular Bioscience (IMB) at The University of Queensland has discovered how cells sacrifice themselves for the greater good if they are infected with a virus, with viral DNA being the key to responding to infection.

Viruses evolve quickly and detecting viral infection is a challenge for the cell, it has recently become apparent that the detection of the genetic material of the virus is a major route through which cells respond to infection.

Dr Kate StaceyInstitute for Molecular Bioscience (IMB) at The University of Queensland

The cell is able to recognise foreign DNA because DNA in mammalian cells is contained within a structure known as the nucleus. The presence of DNA outside the nucleus is a sure sign that something is wrong, and may indicate the presence of a viral invader.

Cellular responses to a virus can include production of anti-viral proteins, but also suicide of the infected cell. By killing itself, the cell can ensure that the virus does not spread throughout the body.

In research published in leading journal Science, Dr Stacey and fellow scientists Dr Tara Roberts and Prof. David Hume and PhD student Adi Idris discovered two proteins in mouse cells, one of which induces cell suicide in response to foreign DNA, and one that prevents it.

AIM2 triggers cell suicide when it senses DNA outside the nucleus, in contrast, a closely-related protein called p202 binds foreign DNA and prevents cell death.

Dr Kate StaceyInstitute for Molecular Bioscience (IMB) at The University of Queensland

The discovery has a range of implications. It will improve understanding of how cells normally combat viral infection, and may also be relevant for the disease lupus, where the immune system attacks normal cellular proteins.

Lupus is a disease with abnormal responses to DNA, and we believe the high levels of p202 found in mouse strains which develop lupus prevent an appropriate response to DNA in the cytoplasm, evidence suggests a similar process occurs in humans, and this research will help explain how lupus develops.

This discovery will also assist in the development of a range of technologies that require the introduction of DNA into cells. This includes gene therapy, where intact genes are introduced into cells of the body to correct genetic abnormalities, and the production of protein drugs by biotechnology.

Dr Kate StaceyInstitute for Molecular Bioscience (IMB) at The University of Queensland

Professor Hume, who in 2007 took up the position of Director of The Roslin Institute at the University of Edinburgh, said this work was the fulfilment of nearly two decades of effort.

We first discovered this response in 1989, and it did not generate much interest. Now we know how it works, the implications in biotechnology, and for understanding autoimmunity and resistance to viral infections are enormous.

Professor David HumeDirector of The Roslin Institute

Professor Hume said he is especially interested in determining how the response varies within and between species and its implications for antiviral immunity.

The research was funded by the National Health and Medical Research Council and the Cooperative Research Centre for Chronic Inflammatory Diseases. Researchers used equipment from the IMB Dynamic Imaging Facility for Cancer Biology, funded by the Australian Cancer Research Foundation.