A study published in Nature details the mechanism used by the herpes virus to wake up and the findings may also be important for long-term covid research.
Chickenpox is a clear example: the cause of itchy blisters on the skin is varicella zoster, one of nine known herpes viruses that can infect and make people sick. It is widespread throughout the world and is best known as a childhood disease. Most of the time, children react well to the infection, and as a reminder, there are scars left, because it is difficult to resist the itch. The virus also does not disappear, which remains latent in the body.
The varicella-zoster variant of the herpes virus lodges in the nerve ganglia. It can reactivate years or decades later and come back as shingles.
Besides varicella zoster virus, the herpes virus family also includes herpes simplex virus types 1 and 2. They are known worldwide to be responsible for painful cold sores and herpes genital. Cytomegalovirus (CMV), also from the same family, is widespread worldwide and can cause serious complications and organ damage, especially in immunocompromised people.
Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus can cause tumors. Human herpesviruses 6 (often divided into A and B) and 7 are also disseminated and trigger, for example, the infantile disease roseola, also known as exanthema subitum.
“The most important thing about herpesviruses is that they remain dormant in the body for life after primary infection,” says Lars Dölken, a virologist at the University of Würzburg, Germany.
Together with fellow researchers, he wanted to understand the mechanism behind the sudden awakening of pathogens. To do this, he took a close look at human herpesvirus 6A (HHV-6A). The research team published the results of the study in the journal Nature. They discovered a previously unknown cellular mechanism that the virus uses to wake up from a dormant state.
From latent to active
People who catch a herpesvirus for the first time often don’t even realize it. The problem is the repeated reactivation of the virus. For this, it often takes advantage of a phase when the host’s immune system is already fighting on other fronts. It can be a cold, as well as strong physical and psychological stress. People living with HIV or transplant patients are particularly susceptible.
HHV-6A settles in the genome of the human cell and survives there in the lag phase until a good opportunity arises for it to attack again and thus multiply. For this, a particular microRNA (or microRNA, in Portuguese) enters the scene and reactivates the virus.
“Almost all herpesviruses generate their own microRNAs, which are extremely important for viruses,” explains virologist Dölken. “[No caso do HHV-6A, verificamos que] If we turn off this viral microRNA, then the virus is – to put it a little loosely – dead. »
And there are indications that the reactivation of other herpes viruses is triggered by the same mechanism.
A viral microRNA as a master regulator
MicroRNA, unlike messenger RNA (mRNA), for example, is not responsible for carrying coding information for specific proteins. Instead, viral microRNAs mediate the metabolism of certain human microRNAs and inhibit their development.
As a result, the production of so-called type 1 interferons is disrupted, messenger substances by which the cell signals the presence of a virus to the immune system.
“But it’s certainly not the only mechanism that’s disrupted,” says Dölken. With his research, he says only the surface of the subject was affected.
Viral microRNAs allow herpes viruses to evade the immune system, or more specifically B and T lymphocytes, which eliminate infected human cells. “These cells recognize proteins foreign to the body, for example those of a virus.”
“However, herpesviruses manage, with the help of ribonucleic acid (RNA or RNA), to reprogram host cells and use them to their advantage without our immune system, that is, B lymphocytes and T, has the chance to recognize the cell as infected,” explains Dölken.
From covid-19 to herpes through the long covid?
The discovery of the crucial viral microRNA, the “master regulator” as Dölken calls it, not only allowed researchers to prevent herpesvirus reactivation in cell culture experiments. Further discoveries and research could also help reactivate dormant cells in the body, which would then be recognized and rendered harmless by the immune system.
“Before transplanting an organ, it would be nice to be able to deactivate dormant cells infected with the herpes virus,” says Dölken.
With their research, virologists could also help solve another problem: the long covid. Because herpesviruses often attack an already weakened immune system, scientists also suspect that they are involved in the various long-term covid patterns.
“An obvious hypothesis is that herpes viruses are reactivated due to coronavirus infection, leading to secondary damage,” says Dölken.
There are still more questions than answers about the long covid, but at least there are already a few prime suspects. The HHV-6 is one of them.