Herpes virus reshapes human DNA within one hour of infection

Viruses have no life of their own. They survive only by entering living cells and stealing what they need. Herpes simplex virus type 1 (HSV-1) is no different.

Known mostly for causing cold sores, this virus is silent in most people. But inside of our cells, the herpes virus does something extraordinary to DNA.

A new study published in the journal Nature Communications shows that HSV-1 does more than hijack the host’s machinery. It reshapes the 3D layout of the human genome. This gives the virus access to specific human genes useful for its own replication.

“HSV-1 is an opportunistic interior designer, reshaping the human genome with great precision and choosing which bits it comes into contact with,” explained Dr. Esther González Almela.

This reshaping is not a side effect; it is intentional. The virus rewires DNA contacts within hours of infection. These changes let HSV-1 build the perfect space to multiply.

How the herpes virus controls DNA

Within one hour of entering the cell, HSV-1 hijacks the host’s RNA polymerase II (RNAP II). This enzyme normally makes RNA from human DNA. The virus redirects it to copy its own genes.

Topoisomerase I (TOP1), which snips DNA to relieve strain, joins the viral effort. Cohesin, which helps fold DNA, also moves toward the viral genome. Together, these enzymes help HSV-1 build viral replication compartments (VRCs).

In these compartments, human transcription slows dramatically. RNAP II and TOP1 abandon host DNA. As a result, chromatin – the tightly packed form of DNA – collapses into a shell just 30% of its normal volume.

VRCs grow quickly. Host DNA is pushed to the edges of the nucleus. Human gene activity plummets. Viral RNA floods the cell within a few hours.

Surprising turns in genome folding

Cohesin partially joins the virus party and forms short loops near viral DNA. But much of its usual function is lost. Some host DNA loops vanish, while others stay intact. The virus rewires specific loops to boost genes it benefits from.

Despite this damage, parts of the human genome resist. A/B compartments – large regions of active or inactive DNA – stay largely intact. This shows that chromatin can keep its broad structure, even under viral attack.

Another twist: HSV-1 does not rely on altering chemical markers like H3K27me3 or H3K9me3. It leaves these epigenetic marks unchanged. Instead, it 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,” noted Dr. Álvaro Castells García from Southern Medical University in Guangzhou, China.

One enzyme blocks the virus

The researchers found a key weakness in the viral plan. Blocking just one host enzyme, TOP1, completely halted HSV-1’s genome reshaping. Without this enzyme, VRCs failed to form. The virus could not make a single new particle.

“In cell culture, inhibiting this enzyme stopped the infection before the virus could make a single new particle,” noted Professor Pia Cosma.

TOP1 is now a potential target for new therapies. Since nearly two-thirds of people under 50 carry HSV-1, a treatment like this could have a huge impact.

The herpes virus rewires DNA

The researchers used advanced tools to uncover HSV-1’s tactics. Super-resolution microscopy let them see features just 20 nanometers wide. Hi-C showed which parts of DNA were in contact.

The virus genome tends to associate with active, gene-rich regions in human DNA. These contacts likely help the virus turn on the genes it needs.

Throughout infection, HSV-1 genome clusters remain stable in size. RNAP II binds closely to them. Cohesin binds loosely. This balance supports ongoing replication.

The findings show that HSV-1 does not just invade. It rewires and reorganizes human cells with precision. Right now, there is no cure for HSV-1. People can treat symptoms, but the virus stays in the body for life. This study shows a new way to fight it.

If we stop the virus from reshaping human DNA early in the infection, we might stop it from spreading which could lead to new treatments.

The study is published in the journal Nature Communications.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–