Layal Liverpool, a DPhil student in the Rehwinkel lab, writes about her research on how cells are able to tell the difference between their own molecules and those of invading viruses.
Every cell in our body is equipped with an alarm system. We can draw an analogy with a smoke alarm, which detects a product of fire – smoke – rather than detecting the fire directly. One of the biggest threats faced by our cells is infection and so, instead of detecting smoke, sensors in our cells are constantly on the look-out for signs of unwanted invaders like viruses. My PhD research is focused on understanding exactly how these sensors in our cells actually recognise invading viruses and what they do about it.
Viruses are packets of genes. They rarely follow the usual rules of biology and so some viruses make their genes out of DNA, like us, whereas others use a sister molecule of DNA called RNA. Either way, when a virus infects one of our cells, its genes are released into the cell. Virus genes are essentially a set of instructions. They tell the cell: “Stop whatever you’re doing and start building viruses instead!” In this way, viruses turn our cells into virus-making factories. Some viruses even burst the cell open when they’re finished, releasing many more viruses into the body in an explosion. These viruses can now spread to infect other cells and make us sick in the process!
Now, it probably sounds as if viruses have a really easy time. They just barge their way into cells and take over. Luckily for us, it is nowhere near that easy. In fact, the very same genes, DNA or RNA, that viruses need to hijack our cells are simultaneously their downfall. This is because sensors in our cells can specifically recognise DNA or RNA from invading viruses and activate the cell’s equivalent of a fire alarm.
In the cell, the fire brigade is an anti-viral molecule called interferon. Interferon gets its name from its ability to interfere with virus infection. It activates a team of other molecules, which work together to stop the virus in its tracks. Just like sprinklers and fire doors would prevent a fire from spreading through a house, interferon can warn surrounding cells that there is a virus around so that they can prepare their anti-viral weapons in advance. This stops the virus from easily spreading to other cells in the body.
Even if the cell can’t handle the virus, it has another strategy. It can commit suicide. Committing suicide might sound like a bad thing, but by killing itself, the cell basically destroys the virus-making factory. The infected cell is actually making a noble sacrifice to protect the rest of the body.
There is one problem that these sensors have to deal with though. The DNA and RNA sensors in our cells recognise genes from viruses, but our own cells have genes too. So how do they tell the difference between our own genes and the virus genes? This matters because if we activate anti-viral responses, like interferon or cell suicide, when there is no virus, this can lead to damage to our own healthy cells. In the same way, you would not want to activate the fire alarm when there is no fire (anyone who has ever burnt toast will relate). In fact, auto-immune or auto-inflammatory diseases such as lupus can result when these same sensors trigger false alarms in response to the cell’s own DNA.
A big part of my research is therefore about understanding exactly how our cells distinguish their own DNA and RNA from virus genes, which are also made of DNA or RNA. One way they tell the difference is through shape. DNA is often depicted as a beautiful ribbon – the classical double helix first discovered by Watson, Crick and Franklin. But DNA and RNA can take different shapes. Another shape they can take is a more jagged, zig-zag shape. Research from our lab and others has found that this zig-zag shape may be recognised by one of the sensors in our cells as a sign of virus infection. In response the cell commits suicide, eliminating the virus-infected cell from the body.
Understanding how our cells recognise and respond to DNA and RNA could help us develop better treatments not only for diseases caused by viruses, where we might want to boost the alarm system in our cells, but also for auto-immune diseases, where we may want to turn off false alarms. When cancer cells die they sometimes release their DNA into the surroundings, where it can be picked up by patrolling immune cells and sensed to activate an anti-cancer alarm. Further investigation of this could therefore offer important insight into on-going research aiming to harness the power of the immune system to fight cancer.
So, next time you’re fighting off a cold, think of it as a fire drill for your cells!