Herpes Virus Rewires Human DNA, Study Reveals
A new study has uncovered how the herpes simplex virus type 1 (HSV-1) manipulates human DNA, potentially paving the way for innovative treatments. The virus, known for causing cold sores, may hold the key to understanding how it spreads and how to stop it.
How the Virus Works
Viruses, lacking independent life, invade cells to survive. HSV-1, commonly causing cold sores, can be dormant in most people. However, inside our cells, this virus significantly alters DNA.
The new study in *Nature Communications* shows HSV-1 does more than just hijack the host’s machinery. It remodels the three-dimensional structure of the human genome. This allows the virus to access human genes that aid its replication.
“HSV-1 is an opportunistic interior designer, reshaping the human genome with great precision and choosing which bits it comes into contact with,”
—Dr. Esther González Almela
These alterations happen intentionally, within hours of infection, facilitating viral multiplication. According to the World Health Organization, approximately 3.7 billion people under 50 globally have HSV-1 (WHO, 2024).
Diving Deeper into the Herpes Virus
HSV-1 often infects during childhood through nonsexual contact. The virus may stay latent in nerve cells, becoming active due to stress, illness, or a weakened immune system.
Besides causing oral lesions, HSV-1 can lead to genital herpes through oral-genital contact. In severe cases, it can cause encephalitis, a potentially fatal brain inflammation, particularly in infants or those with weakened immune systems.
The Virus’s DNA Control
HSV-1 takes over the host’s RNA polymerase II (RNAP II) within an hour of entering the cell. This enzyme usually creates RNA from human DNA. The virus redirects it to copy its own genes.
Topoisomerase I (TOP1), which cuts DNA to relieve strain, joins in. Cohesin, which folds DNA, also moves toward the viral genome. Together, these enzymes help HSV-1 build viral replication compartments (VRCs).
Human transcription slows in these compartments. RNAP II and TOP1 leave host DNA. Consequently, chromatin, the tightly packed DNA form, collapses.
Unexpected Genome Folding Changes
Cohesin forms short loops near the viral DNA. However, much of its usual function is lost. The virus rewires specific loops to boost genes it benefits from.
A/B compartments, which are large regions of active or inactive DNA, remain largely intact. The virus does not rely on altering chemical markers like H3K27me3 or H3K9me3, but changes the physical shape and positioning of DNA.
“We always thought dense chromatin shut genes down but here we see the opposite: stop enough transcription first and the DNA compacts afterwards. The relationship between activity and structure might be a two-way street,”
—Dr. Álvaro Castells García from Southern Medical University
Halting the Virus
Researchers identified a weakness in the viral plan. Blocking TOP1 stopped HSV-1’s genome reshaping, preventing new particle formation.
“In cell culture, inhibiting this enzyme stopped the infection before the virus could make a single new particle,”
—Professor Pia Cosma
TOP1 is now a potential target for new treatments. Since nearly two-thirds of people under 50 carry HSV-1, a treatment like this could have a huge impact.
How the Virus Rewires DNA
Researchers used advanced tools like super-resolution microscopy and Hi-C to study HSV-1’s strategies. The viral genome associates with active, gene-rich regions in human DNA, which helps the virus turn on the genes it needs.
HSV-1 genome clusters remain stable during infection, with RNAP II and cohesin binding closely. These findings reveal HSV-1’s precision in reorganizing human cells. Since there’s no current cure, this study could open new treatment avenues.
If the virus is stopped early, it may prevent spread. This could lead to new treatments.
