Researchers from Germany’s Julius-Maximilians-Universität (JMU) Wurzburg have revealed a cellular mechanism that human herpesvirus 6 (HHV-6) relies on to reactivate.
Herpes viruses are just about universal in human beings. There are eight known types to date, and many people have at least one variety living in them. The microbes remain in the body after infection, emerging from time to time to replicate and attack cells under favorable conditions.
Symptoms that may be observed when herpes viruses awaken from dormancy include shingles, cold sores, and genital herpes. When done with their damage, they go back to their latent state waiting for another opportunity to emerge again.
Scientists have now discovered that a viral microRNA is at the center of episodic reawakening. Many herpesviruses have over time developed the ability to take advantage of host cells with the aid of tiny RNA molecules.
Findings from this new study, led by researchers Bhupesh Prusty and Lars Dölken, were published in Nature.
Hazards of herpes virus awakening
According to researchers, at least 9 in every 10 persons have HHV-6 in their bodies. Most people are not aware of this, however, since the virus does not always cause problems. Issues only arise occasionally when they rouse from dormancy.
“How herpes viruses reactivate from a dormant state is the central question in herpesvirus research,” said Dölken, a virologist at JMU. “If we understand this, we know how to intervene therapeutically.”
The reawakening of the HHV-6 has been linked to weakened heart function and transplanted organ rejection. It is also thought to be a factor in conditions such as multiple sclerosis (MS) and myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS).
In addition, newer research shows that HHV-6 may play a part in nervous system disorders, including schizophrenia and bipolar disorder.
How reactivation occurs
Researchers found that a microRNA called miR-aU14 drives the reawakening of HHV-6. The virus produces this small RNA molecule by itself.
This microRNA disrupts the metabolism of microRNAs in humans after its expression. It, thus, selectively inhibits the maturation of some human microRNAs belonging to the miR-30 family.
This JMU research is the first to confirm that a microRNA can have a direct say in how the maturation of other microRNAs takes place.
When released into a cell, the viral microRNA messes up the former’s mitochondria and causes them to split. This makes the cell stop producing type I interferons, substances needed to signal viral invasion to the immune system.
With the interferons thus curtailed, HHV-6 gets the freedom to become active, replicate, and cause problems unhindered. Researchers found that the viral microRNA plays a direct role in triggering virus reactivation.
The findings in this study are promising for the development of new therapeutics. It suggests the possibility of turning off members of different microRNA families with the aid of small, man-made RNA molecules.
Now, the Wurzburg team is seeking to figure out the specific mechanism used by miR-aU14 to trigger viral reactivation. This information could go a long way in helping to decide the right approaches to adopt for regulating the reactivation of viruses for therapeutic reasons. There are signs that other herpes viruses may also awaken using this same mechanism. The researchers are looking to better grasp the molecular effects of mitochondrial fragmentation as well.