# Nucleus softens during herpesvirus infection

## TL;DR

This study shows that the nucleus becomes softer during herpesvirus infection, revealing how viral infections alter cell mechanics.

## Contribution

The paper reveals that herpesvirus infection causes nuclear softening due to reduced outward forces and low-density viral replication compartments.

## Key findings

- The nucleus softens during herpes simplex virus type 1 infection.
- The viral replication compartment has low biomolecular density, contributing to nuclear softening.
- Reduced outward forces like cytoskeletal pull and osmotic pressure explain decreased nuclear stiffness.

## Abstract

Nuclear mechanics is remodeled not only by extracellular forces but also by internal modifications, such as those induced by viral infections. During herpes simplex virus type 1 infection, the nuclear structures undergo drastic reorganization, but little is known about how nuclear mechanobiology changes as a result. We show that the nucleus softens dramatically during the infection. To understand the phenomenon, we used advanced microscopy and computational modeling. We discovered that the enlarged viral replication compartment had a low biomolecular density, partially explaining the observed nuclear softening. The mobility of the nuclear lamina decreased, which suggests increased rigidity and an inability to induce softening. However, computational modeling supported by experimental data showed that reduced outward forces, such as cytoskeletal pull and intranuclear osmotic pressure acting both on and within the nucleus, can explain the decreased nuclear stiffness. Our findings reveal that during infection, the nucleus is subject to changes in multiple mechanical forces, leading to decreased nuclear stiffness.

DNA viruses take over the host cell nucleus, inducing dramatic structural modifications. There is currently very little knowledge of how the progression of viral infection modifies the mechanical properties of the nucleus, which are essential for various cellular processes, including gene expression and cell migration. Here, we show that the nucleus softens when herpesvirus infection progresses. We discovered that the viral replication compartment established in the central parts of the nucleus had a low biomolecular density, which may contribute to the nuclear softening. The shape and motion of the nuclear lamina suggested that it became more rigid, indicating that another mechanism was involved in the decreased elasticity. Our mechanical simulations and experiments showed that a reduction in outward forces, such as actin cytoskeleton pull or osmotic pressure, is the most likely factor in the nuclear softening. Our study provides new insights into the effects of DNA viruses on the mechanics of host cell nuclei, significantly expanding the knowledge of viral infection mechanobiology.