# Visualization of Molluscum Contagiosum Virus in FFPE Skin Sections Using NanoSuit‐CLEM: Ultrastructural Evidence of Viral Spread via Skin Barrier Disruption

## TL;DR

This study shows how the Molluscum contagiosum virus spreads through damaged skin using a new imaging technique, highlighting the importance of skin barrier integrity.

## Contribution

The study introduces NanoSuit-CLEM as a novel method to visualize Molluscum contagiosum virus in FFPE skin samples, revealing viral localization and transmission mechanisms.

## Key findings

- MC virus particles are densely localized in the stratum corneum but do not invade deeper layers in intact skin.
- Viral penetration occurs in areas of epidermal disruption, such as damaged stratum corneum.
- NanoSuit-CLEM provides detailed visualization of mature virus particles and their distribution.

## Abstract

Molluscum contagiosum (MC) is a common viral skin infection caused by members of the Poxviridae family. It primarily affects children, sexually active adults, and immunocompromised individuals. Although MC spreads through direct contact and auto‐inoculation, the precise mechanisms by which the virus penetrates the skin barrier remain poorly understood.

We applied NanoSuit‐correlative light and electron microscopy (NanoSuit‐CLEM) to formalin‐fixed paraffin‐embedded (FFPE) skin sections to visualize MC virus particles in situ with high resolution. Melan‐A immunohistochemistry using 3,3′‐diaminobenzidine (DAB) with osmium staining was performed to identify Henderson–Patterson bodies.

Ultrastructural analysis revealed that MC virus particles were densely localized in the stratum corneum but did not invade deeper epithelial layers in intact skin. However, in areas of epidermal disruption, such as detached or damaged stratum corneum, the virus was observed penetrating into lower layers. While Melan‐A immunostaining successfully detected Henderson–Patterson bodies, it failed to identify mature MC virus particles. In contrast, NanoSuit‐CLEM combined with Mayer's hematoxylin and lead staining enabled detailed visualization of mature viral particles and their distribution within the stratum corneum.

These findings provide direct ultrastructural evidence that MC virus entry occurs through compromised skin, underscoring the crucial role of the stratum corneum in barrier function. This study highlights the importance of preventing mechanical skin injury, such as scratching or shaving, to limit MC transmission. NanoSuit‐CLEM offers a powerful new tool for studying viral pathogenesis in archival tissue samples.

Molluscum contagiosum (MC) virus, a member of the Poxviridae family, primarily spreads through skin contact, with disrupted skin serving as a key entry point. Using NanoSuit‐correlative light and electron microscopy (CLEM), we visualized MC virus particles densely packed in the stratum corneum but not penetrating intact epithelial layers. This study highlights the role of skin injury in MC transmission and provides a novel method for precise viral mapping, contributing to improved prevention strategies.