From chickenpox to shingles: new insights
The virus that causes chickenpox can also lead to more serious and painful conditions in older people. An EU-funded researcher is discovering how the virus interacts with the immune system and, possibly, how it might be controlled.
© ÐšÐ¸Ñ€Ð¸Ð»Ð» Ð Ñ‹Ð¶Ð¾Ð² - fotolia.com
Chickenpox is regarded a harmless childhood disease but in later life it can lead to painful conditions such as shingles (zoster) or neuralgia. It is caused by the varicella zoster virus.
A varicella infection first takes hold in the respiratory tract but then spreads to the white blood cells called leucocytes which in turn carry it around the body producing the characteristic skin rash of chickenpox. Ultimately the virus infects nerve cells where it can remain hidden for many decades.
“Most of us are infected with the virus,” says Abel Viejo-Borbolla, of Hannover Medical School, who is a fellow in the EU-funded INMA project. “Approximately half will develop shingles by the age of 85, and 15 % of that half will then have post-herpetic neuralgia which is the second most common type of neuropathic pain worldwide. It can last for months or even more than a year and is very painful and there are no optimal treatments.”
White blood cells
Viejo-Borbolla’s team is investigating how the virus is able to infect the white blood cells. Their focus is on chemokines, small protein molecules that help guide white blood cells to the site of an infection or tissue damage. The group speculated that the virus is somehow modulating the activity of the chemokines to direct white blood cells towards itself. But how?
They found that a molecule called glycoprotein C, located on the surface of the varicella virus, not only binds tightly to chemokine molecules but also seems to stimulate chemokine activity and attract white blood cells.
“When we put the glycoprotein C together with the chemokine we have three or five times more leucocytes migrating,” says Viejo-Borbolla. “So we hypothesise though we have not proven it that this might facilitate the spread of the virus.”
The next step is to investigate how glycoprotein C affects chemokine activity. If the interaction could somehow be blocked it may be possible to limit the infection of the white blood cells.
Hope for better treatments
Chemokines are also implicated in the spread of cancer cells within the body, so improved knowledge of how chemokines interact with other molecules, and how their activity is increased, could lead to the discovery of an inhibitor molecule that would slow the spread.
In parallel work, the team is investigating how varicella infects nerve cells, modulates their activity and causes pain. “If we could understand the molecular mechanisms of induction of pain by this virus it might help us understand pain induction in other painful diseases, such as cancer or diabetes.”
They are also studying how the virus can remain latent within nerve cells for so long. Uncovering the mechanism may open the way to antiviral drugs that could block those processes. It could also lead to safer vaccines. A weakened strain of the varicella virus is used as a vaccine against chickenpox, but it, too, can cause shingles in later life, especially in people with weakened immune systems.
Viejo-Borbolla’s project is supported by the EU’s Marie SkÅ‚odowska-Curie fellowship programme which, he says, was essential to the work starting at all. “Before I came to Hannover I did not have experience with the varicella zoster virus. The grant allowed me to investigate different aspects I could not have investigated otherwise,” he says.