Chicken pox is a prime example: the source of the itchy blisters is one of the nine known herpes viruses: shingles. Chickenpox is widespread throughout the world, and is well known as a childhood disease. Most of the time, children outgrow the infection, but there may be some scarring. The virus stays in the body for life.
The herpes zoster virus variant settles in the ganglia, groups of nerve cells in the peripheral nervous system. And it can resurface years or decades later.
In addition to the virus that causes chickenpox, the herpes family of viruses includes herpes simplex viruses, types 1 and 2. Both are responsible for painful cold sores and genital herpes. Cytomegalovirus, another genus of herpes virus, is also widespread and can cause serious complications and organ damage, especially in immunosuppressed people.
Epstein-Barr virus and Kaposi’s sarcoma-associated herpes virus, in turn, can cause tumors. Human herpes viruses 6 (often subdivided into A and B) and 7 are also widespread and cause, for example, “three-day fever”, a childhood disease.
“The most important thing about herpes viruses is that they remain dormant in the body for life after primary infection,” explains Lars Dölken, a virologist at the University of Würzburg, to DW. Dölken thus names the most important common characteristic of this family of viruses. His team tries to understand the mechanism behind the sudden awakening of the pathogens, and to do so they have carefully studied the human herpesvirus 6A (HHV-6A). Scientists have discovered a hitherto unknown cellular mechanism that the virus uses to wake up, as published in the journal Nature.
When the immune system fights on other fronts
People who get the herpes virus for the first time often hardly notice it. The problem is usually the repeated reactivation of the virus. To do this, it usually uses a phase in which the host’s immune system is already fighting on other fronts. That can be a cold, as well as strong physical and psychological stress. People with HIV and transplant patients are especially susceptible.
HHV-6A is incorporated into the genome of the human cell and survives there in the latency phase, until a good opportunity presents itself for the virus to attack again and multiply. Then a certain micro-RNA – a small RNA molecule involved in various biological processes – reactivates the virus.
“Almost all herpes viruses make their own micro-RNAs, which are extremely important for viruses. But there is no example of a herpes virus in which the micro-RNA is so fundamental,” says virologist Dölken. “If we turn off this viral micro-RNA, then the virus is – to put it loosely – dead.”
Manifestation of herpes zoster, known as “shingles”, an annoying disease that attacks nerve cells
A viral micro-RNA as a master key
Micro RNA, unlike mRNA, for example, is not responsible for carrying the blueprints for specific proteins: it is one of the non-coding RNAs. In contrast, the viral microRNA intervenes in the metabolism of certain human micro-RNAs and inhibits their development.
As a result, the production of so-called type I interferons is disturbed. These are messenger substances with which the cell signals the presence of viruses to the immune system. “But this is not the only mechanism that is altered,” adds Dölken.
Viral micro-RNA makes it possible for herpes viruses to escape the immune system, or more precisely, the B and T cells that kill infected human cells. “These cells recognize proteins that are foreign to the body, such as those of a virus.
“However, with the help of RNA, herpesviruses manage to reprogram host cells and use them to their advantage, without our acquired immune system, that is, B and T cells, having the opportunity to recognize the cell as infected,” explains Dölken.
From COVID-19 to herpes and prolonged COVID
The discovery of the crucial viral microRNA, the “master regulator,” as Dölken calls it, not only made it possible for researchers to prevent herpes virus reactivation in cell culture experiments.
The discoveries and new research could also help in the future to reactivate dormant cells in the body, which the immune system could recognize and deactivate without harming them. “Before transplanting an organ, it would be nice to be able to disconnect the cells infected by the herpes virus,” stresses Dölken.
The Würzburg virologists could also contribute to solving another problem: prolonged COVID. Since herpes viruses often attack an already weakened immune system, scientists also suspect that they are involved in the different disease patterns of prolonged COVID. “An obvious assumption is that herpes viruses are reactivated due to infection with the coronavirus, which causes secondary damage,” says Dölken. There are still more questions than answers. But at least the main suspects have been identified: HHV-6 is one of them.