Have you ever seen a tenant who is not satisfied with occupying a room, but demands to repaint the entire house?Herpes simplex It does something similar to our cells, only instead of repainting the walls, it completely remodels the architecture of our DNA.
The researchers of Center for Genomic Regulation in Barcelona they discovered that this virus does not just replicate: In just a few hours, it transforms the three-dimensional structure of the human genome, compressing it to 70% of its original volume and moving it to the edges of the cell nucleus. All to make room for their own replication factory. But there is good news: they have also found a way to stop it..
Herpes simplex, a molecular architect in our DNA
Herpes simplex virus type 1 (HSV-1) causes those annoying blisters we know as cold sores, but its true abilities go far beyond simple tissue damage. Esther Gonzalez-Almela e Alvaro Castells Garcia, the first authors of the study published Nature Communications., used a combination of super-resolution microscopy and chromosome capture techniques to unravel this hidden mechanism.
The virus begins its restructuring work within the first hour of infection. Literally steals RNA polymerase II, the enzyme essential for the transcription of human genes, by hijacking it to its own replication compartments. With this large-scale theft, the virus causes the transcriptional collapse of the entire host genome.
Our genome, normally organized in an open and accessible structure, is compressed into a dense shell that occupies only 30% of the original volume.
Topoisomerase: The Master Switch
The real stroke of genius of the research lies in having identified the enzyme topoisomerase I as the nerve center of the entire operation. This enzyme, which normally cuts DNA to release tension during replication, is recruited by the virus along with other structural proteins such as cohesin.
Maria Pia Cosma, ICREA researcher and corresponding author of the study at the Center for Genomic Regulation, explained how this enzyme became the Achilles heel of the virus:
“In cell cultures, inhibiting this enzyme stopped infection before the virus could produce a single new particle.”
How Genomic Sequestration Works
Within three hours of infection, most of the polymerase and a considerable fraction of other key factors completely abandon the human genes. This mass theft causes transcription to collapse throughout the host genome, which in turn causes chromatin to be compressed into a dense shell.
What makes this discovery special is that overturns our understanding of the relationship between DNA structure and function. We used to think that dense chromatin automatically turned off genes, but here we see the opposite: if enough transcription stops, the DNA compacts accordingly.
Herpes simplex, as mentioned, physically shifts the human genome towards the edges of the nucleus, freeing up central space to set up its own viral replication factory. It's a bit like evicting all the tenants from a building to turn it into an illegal factory.
Herpes simplex, the impact on 4 billion people
Herpes simplex affects nearly 4 billion people under 50 all over the world. Two out of three people live with HSV-1 their entire lives, although in most cases the infection remains asymptomatic. When it does occur, it can cause not only cold sores, but also blindness or life-threatening diseases in newborns and immunocompromised people.
The recently published research opens up new therapeutic possibilities precisely because it identifies a single point of vulnerability. While current treatments can only manage the symptoms, Drug-resistant strains are on the rise and there is still no definitive cure.
A concrete hope
The discovery that a single enzyme controls the virus's entire ability to rearrange the human genome offers us a completely new therapeutic target. It is much simpler to develop drugs that specifically inhibit topoisomerase I than to try to block every single aspect of viral replication.
The team of the Center for Genomic Regulation used techniques that can “see” structures just 20 nanometers wide, about 3.500 times thinner than a human hair, to observe this process in real time.
We’re not ready for clinical trials yet, but this research completely changes the way we look at herpes simplex. It’s no longer just a virus that hides in neurons and reappears when we least expect it. It’s a sophisticated manipulator of our own genetic code, but we now know exactly what switch to flip to stop it.
