The Secret to Herpesvirus Awakening

The Secret to Herpesvirus Awakening ...

Eight different herpes viruses are known to date in humans. They all settle down permanently in the body after an acute infection. Under certain circumstances, they wake up from this naive phase, multiply and attack other cells. This reactivation is often associated with symptoms, such as stale cold sores or shingles.

Most herpesviruses have learned to use small RNA molecules, so-called microRNAs, to reprogram their host cells to their advantage. In the journal Nature, researchers demonstrate the previously unknown cellular mechanism by which human herpesvirus 6 (HHV-6) awakens.

Problems after reactivation of the virus

HHV-6 is thought to be infected by more than 90% of people without seeing it. It is unlikely that the virus will cause problems only when it wakes up repeatedly.

HHV-6 reactivation is suspected to be ineffective in regulating heart function, causing transplanted organs to be rejected, and triggering diseases such as multiple sclerosis or chronic fatigue syndrome (ME/CFS). Other factors are also suggested that this herpesvirus may be involved in the development of schizophrenia, bipolar disorder, and other disorders of the nervous system.

"How herpesviruses react from a dormant state is the central issue," says a JMU virologist. "If we understand this, we know how to intervene therapeutically." "It is the reactivation of HHV-6, according to the previously unknown key.

What the microRNA does in the cell

The regulatory miR-aU14 comes from the virus itself. As soon as it is expressed, it interferes with human microRNA metabolism. In doing so, it selectively interferes with the maturation of several important cellular microRNAs of the miR-30 family. This in turn affects a cellular signaling pathway, the so-called miR-30 / p53 / Drp1 axis.

The viral miR-aU14 stimulates mitochondrial fragmentation. These cell structures are of paramount importance for energy production, but also for signal transmissions in the defense against viruses.

The viral miR-aU14 interferes with the production of type I interferons messenger substances with which the cell signals the presence of viruses to the immune system. However, the herpesvirus is able to transition from a dormant to an active state, triggering the reactivation of the virus.

How the research continues

The researchers are now attempting to understand the exact mechanism by which the viral microRNA initiates the reactivation of the virus. Moreover, there are first indications that other herpesviruses may be reactivated via the same mechanism. This might further reveal therapeutic strategies to either prevent the reactivation of these viruses or to specifically trigger it in order to then eliminate the reactivating cells.

For the first time, this research from Wurzburg shows that a microRNA can directly control the maturation process of other microRNAs. This also opens new therapeutic possibilities: Artificial small RNAs can be customized to specifically distinguish between individual members of microRNA families. This was previously impossible.

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