March 29, 2024

How Herpes Viruses Trigger Their Own Awakening

HHV-6 reactivation is suspected of hindering heart function, triggering the rejection of transplanted organs, and triggering diseases such as numerous sclerosis or chronic tiredness syndrome (ME/CFS). In addition, current studies recommend that this herpesvirus might be associated with the development of schizophrenia, bipolar disorder, and other illness of the anxious system.
” How herpesviruses reactivate from an inactive state is the central concern in herpesvirus research study,” says JMU virologist Lars Dölken. A formerly unknown key to this is a viral microRNA called miR-aU14.
What the microRNA performs in the cell
The regulative miR-aU14 originates from the infection itself. As quickly as it is revealed, it disrupts the metabolic process of human microRNAs. In doing so, it selectively interferes with the maturation of a number of microRNAs of the miR-30 family. As an outcome, these essential cellular microRNAs are no longer produced. This in turn impacts a cellular signaling pathway, the so-called miR-30/ p53/ Drp1 axis.
Through this path, the viral miR-aU14 causes mitochondrial fragmentation. These cell structures are of main value for energy production, however also for signal transmissions in the defense against infections.
The viral miR-aU14 therefore hinders the production of type I interferons– messenger compounds with which the cell signifies the presence of infections to the immune system. Since the interferons are missing, the herpesvirus has the ability to switch from a dormant to an active state undisturbed. Interestingly, the Würzburg research study group was also able to show that the viral microRNA is not only vital for infection replication, but likewise directly sets off the reactivation of the virus from its dormant state.
How the research study continues
The scientists now desire to comprehend the specific mechanism by which the viral microRNA starts the reactivation of the virus. This could expose restorative options to either prevent reactivation of these viruses or to particularly trigger it in order to then eliminate the reactivating cells.
For the very first time, this work from Würzburg shows that a microRNA can directly control the maturation procedure of other microRNAs. This also opens up brand-new healing possibilities: Artificial little RNAs can be designed to specifically switch off private members of microRNA families. Such subtle interventions were not possible previously.
Referral: “Selective inhibition of miRNA processing by a herpesvirus-encoded miRNA” by Thomas Hennig, Archana B. Prusty, Benedikt B. Kaufer, Adam W. Whisnant, Manivel Lodha, Antje Enders, Julius Thomas, Francesca Kasimir, Arnhild Grothey, Teresa Klein, Stefanie Herb, Christopher Jürges, Markus Sauer, Utz Fischer, Thomas Rudel, Gunter Meister, Florian Erhard, Lars Dölken and Bhupesh K. Prusty, 4 May 2022, Nature.DOI: 10.1038/ s41586-022-04667-4.
Cooperation partners and sponsors.
Numerous groups at JMU are conducting interdisciplinary research study on this topic. They originate from the Institute of Virology and Immunobiology, the Biocentres Chairs of Biochemistry, Biotechnology and Biophysics, and Microbiology, the Rudolf Virchow Centre and the Helmholtz Institute for RNA-based Infection Research. Researchers from the Free University of Berlin and the University of Regensburg were likewise involved.
The research study was moneyed by the Helmholtz Institute for RNA-based Infection Research, the Solve ME/CFS Initiative (USA), the HHV-6 Foundation (USA), the Amar Foundation (USA) and by the European Research Council within the structure of an ERC grant.

Fragmentation of mitochondria (green): The Drp-1 proteins responsible for the decay are labeled with antibodies and stained in magenta. Credit: Chair of Virology/ University of Wuerzburg
8 various herpes viruses are understood to date in humans. This reactivation is typically associated with signs, such as scratchy cold sores or shingles.
In the course of evolution, most herpesviruses have learned to utilize little RNA particles, so-called microRNAs, to reprogram their host cells to their benefit. A research group led by Bhupesh Prusty and Lars Dölken from Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, has actually now had the ability to reveal for the very first time that a viral microRNA functions as a master regulator to cause the reactivation of the virus In a study released today (May 4, 2022) the journal Nature, the researchers provide the formerly unidentified cellular mechanism by which human herpesvirus 6 (HHV-6) triggers its own awakening.
Issues after reactivation of the virus.
More than 90 percent of all people are contaminated with HHV-6 without seeing it. The infection most likely just causes problems when it gets up repeatedly.

Human herpesvirus 6 (HHV-6) is the common cumulative name for human betaherpesvirus 6A (HHV-6A) and human betaherpesvirus 6B (HHV-6B). HHV-6 (and HHV-7) levels in the brain are also elevated in people with Alzheimers disease. HHV-6B primary infection is the cause of the typical childhood disease exanthema subitum (also understood as roseola infantum or 6th illness).

Eight various herpes viruses are known to date in humans. The regulatory miR-aU14 comes from the infection itself. The viral miR-aU14 hence interferes with the production of type I interferons– messenger compounds with which the cell signals the existence of viruses to the immune system. Remarkably, the Würzburg research study group was also able to reveal that the viral microRNA is not just important for infection duplication, but also directly sets off the reactivation of the infection from its inactive state.
The researchers now want to understand the exact mechanism by which the viral microRNA starts the reactivation of the infection.