Biology subjects

Aho, V.

Publications and source records attributed to Aho, V..

3 recordsLinked to original sources

bioRxiv2025

Nucleus softens during herpesvirus infection

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. Author SummaryDNA 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.

cell biology↗

bioRxiv2023

Progression of herpesvirus infection remodels mitochondrial organization and metabolism

Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized at the perinuclear area, a significant increase in the number and clustering of ER-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.

microbiology↗

bioRxiv2022

Parvovirus infection alters the nucleolar structure

The nucleolus is a biomolecular condensate essential for ribosome biogenesis and cellular stress response, and it is a key target for many DNA viruses. However, little is known about how autonomous parvovirus infection impacts nucleolar structure and function. Here, we used advanced imaging techniques, including ten-fold robust expansion microscopy (TREx), cryo soft X-ray tomography (Cryo-SXT), and interactomics and biochemical approaches, to study nucleolar remodeling during canine parvovirus infection. Infection led to redistribution of nucleolar upstream binding transcription factor 1 (inner core), fibrillarin (middle layer), and Ki-67 (outer rim). In contrast, peripheral nucleolar proteins (nucleolin and nucleophosmin) and precursor ribosomal RNAs (pre-rRNAs) remain in circularized structures. TREx and Cryo-SXT microscopy revealed profound nucleolar structural changes, including thickened perinucleolar chromatin and enlarged nucleolar low-protein density channels. BioID identified interactions between viral NS2 and nucleolar proteins in ribosome biogenesis. Northern blotting demonstrated a slowdown in ribosome biogenesis during infection. Collectively, these findings provide novel insights into how parvoviruses remodel nucleolar structure and function.

cell biology↗