Herpes Virus Speeds Multiplication by Fluidizing Nuclei

New study reveals how herpes simplex virus uses a protein to make the human cell nucleus more fluid-like, enabling faster viral replication.

Published on Mar. 6, 2026

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Researchers at NYU Langone Health have found that the herpes simplex virus uses a protein called infected cell protein 4 (ICP4) to partially liquefy the tightly packed, gel-like interior of human cell nuclei. This fluidization of the nucleus makes it easier for the virus to replicate itself more quickly. The study revealed that blocking ICP4's ability to fluidize the nuclear compartment caused a four-fold drop in the production rate of new viral copies.

Why it matters

The physical state of the cell nucleus is a fundamental barrier that viruses must overcome to multiply. By studying how viruses manipulate cells, researchers can uncover fundamental rules of biology that could lead to new ways to counter viral replication. Understanding the mechanisms used by the highly prevalent herpes simplex virus could provide insights applicable to other viruses that replicate in the nucleus.

The details

The researchers engineered cells to produce glowing protein nanoparticles called nucGEMs, which they used to track the degree of motion in the nuclear environment as a measure of its thickness. When the cells were infected with herpes simplex virus 1, the glowing particles bounced around much more, indicating the nucleus had become more fluid-like. The study found that the viral protein ICP4 attaches to chromatin remodeling protein complexes, causing the unwinding of DNA around histones without enabling transcription. This chromatin motion changes the physical properties of the nucleus, loosening the interior to allow for the growth of viral condensate factories needed for efficient viral replication.

  • The study was published online on March 5, 2026.

The players

Liam Holt

A professor in the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health and faculty in the Institute for Systems Genetics, and the senior study author.

Nora Herzog

A recent graduate from the biomedical sciences program at NYU Langone, and now a postdoctoral fellow at Universitat de València Parc Cientific in Valencia, Spain, who was the first study author.

NYU Langone Health

A fully integrated health system that consistently achieves some of the lowest mortality rates in the nation, and where the research was conducted.

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What they’re saying

“The physical state of the nucleus is a fundamental barrier that a virus must overcome to multiply. Viruses are masters at manipulating cells, and by studying their tricks, we uncover fundamental rules of biology.”

— Liam Holt, Professor, Department of Biochemistry and Molecular Pharmacology, NYU Langone Health (Molecular Cell)

“We are working now to confirm the mechanism by which ICP4 fluidizes the nucleus, which could give us new, specific targets to physically counter viral replication. We will also be looking to see if this mechanism is used by other viruses that replicate in the nucleus, from the double-stranded DNA viruses responsible for shingles to RNA viruses like influenza virus to retroviruses like HIV.”

— Nora Herzog, Postdoctoral Fellow, Universitat de València Parc Cientific (Molecular Cell)

What’s next

The research team plans to further investigate the mechanism by which the viral protein ICP4 fluidizes the cell nucleus, with the goal of identifying new targets to counter viral replication. They also intend to examine whether this mechanism is used by other viruses that replicate in the nucleus.

The takeaway

This study provides important insights into how viruses, such as the highly prevalent herpes simplex virus, manipulate the physical properties of the cell nucleus to enable more efficient viral replication. By understanding these fundamental biological mechanisms, researchers may be able to develop new strategies to disrupt viral multiplication and improve treatments for viral infections.