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Uncovering Viral Dose–Driven Control of Herpesvirus DNA Replication and Infection-Induced Nuclear Damage

Cegielski, Blazej (2025) MOBN03 20242
Degree Projects in Molecular Biology
Abstract
Herpes simplex virus type 1 (HSV-1) is a widespread DNA virus capable of establishing lifelong infections and eliciting diverse disease outcomes. The amount of virus that initially enters a cell, known as the multiplicity of infection (MOI), plays a critical role in shaping infection dynamics. However, its influence on virus–host interactions at the single-cell level remains to be fully elucidated.

In this study, we explored how varying levels of viral input affect infection progression in individual human cells. Using fluorescent tagging and time-resolved imaging, we observed that higher viral input leads to more rapid viral activity and notable changes in the organisation of nuclear material. As the infection progresses, the... (More)
Herpes simplex virus type 1 (HSV-1) is a widespread DNA virus capable of establishing lifelong infections and eliciting diverse disease outcomes. The amount of virus that initially enters a cell, known as the multiplicity of infection (MOI), plays a critical role in shaping infection dynamics. However, its influence on virus–host interactions at the single-cell level remains to be fully elucidated.

In this study, we explored how varying levels of viral input affect infection progression in individual human cells. Using fluorescent tagging and time-resolved imaging, we observed that higher viral input leads to more rapid viral activity and notable changes in the organisation of nuclear material. As the infection progresses, the structural arrangement within the nucleus becomes increasingly altered, eventually compromising nuclear integrity in a manner that depends on the level of viral exposure.

Our observations suggest a dose-dependent relationship between viral input and nuclear architecture changes, with implications for how cells respond to and are impacted by infection. These findings underscore the significance of viral load in determining the cellular outcomes of HSV-1 infection and contribute to a better understanding of virus–host dynamics. (Less)
Popular Abstract
When Numbers Matter: How Many Viruses Change the Fate of an Infected Cell

How much does the number of invaders matter in a microscopic battle? Herpes simplex virus type 1 (HSV-1), a virus known for causing cold sores in most, but also more severe encephalitis and keratitis in others, offers a fascinating answer. While most research focuses on how a single virus infects a cell, or how many viruses infects a population, this project set out to understand what happens when one, a few, or many viruses attack single cell at once.

To achieve this, we combined engineered virus and fluorescent tagging system to mark each incoming viral genome with a red glow, making it possible to follow the path and fate of every virus inside living cells,... (More)
When Numbers Matter: How Many Viruses Change the Fate of an Infected Cell

How much does the number of invaders matter in a microscopic battle? Herpes simplex virus type 1 (HSV-1), a virus known for causing cold sores in most, but also more severe encephalitis and keratitis in others, offers a fascinating answer. While most research focuses on how a single virus infects a cell, or how many viruses infects a population, this project set out to understand what happens when one, a few, or many viruses attack single cell at once.

To achieve this, we combined engineered virus and fluorescent tagging system to mark each incoming viral genome with a red glow, making it possible to follow the path and fate of every virus inside living cells, from its entry to a violent climax in nucleus rupture. By varying the ratio of infectious viruses to each cell—a parameter known as multiplicity of infection (MOI)—we could precisely compare infection scenarios ranging from less than a single infectious virus per cell, to a full-scale invasion.

The analysis revealed that the number of infecting viruses fundamentally alters the infection process. At low MOI, each viral genome typically establishes its own replication compartment—specialised regions inside the cell nucleus where the virus accumulates its machinery and replicates. As the number of incoming viruses increases, these compartments form earlier and grow faster, but interestingly, the cell cannot keep up with the increased demand. Physical limitations leading to saturation of cells and inhibitory effects mean that only a subset of viruses successfully establish these replication sites, regardless of how many try.

As the viral load rises, the virus’s activity pushes the cell’s own genetic material aside, counterintuitively eventually causing the nucleus to shrink rather than swell and ultimately leading to nucleus’ rupture. This finding demonstrates that not just the presence, but the quantity of infecting viruses dramatically shapes the course and outcome of infection.

By illuminating how cells respond to different levels of viral attack, this research helps us understand the strategies viruses use to hijack and reshape their hosts. Such insights could ultimately inform new ways to block viral infection at its earliest and most critical steps.

Master’s Degree Project in Molecular Biology, 60 credits 2025
Department of Biology, Lund University
Supervisor: Alex Evilevitch
Virus Biophysics Unit (Less)
Please use this url to cite or link to this publication:
author
Cegielski, Blazej
supervisor
organization
course
MOBN03 20242
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9214491
date added to LUP
2025-10-24 13:19:53
date last changed
2025-10-24 13:19:53
@misc{9214491,
  abstract     = {{Herpes simplex virus type 1 (HSV-1) is a widespread DNA virus capable of establishing lifelong infections and eliciting diverse disease outcomes. The amount of virus that initially enters a cell, known as the multiplicity of infection (MOI), plays a critical role in shaping infection dynamics. However, its influence on virus–host interactions at the single-cell level remains to be fully elucidated.

In this study, we explored how varying levels of viral input affect infection progression in individual human cells. Using fluorescent tagging and time-resolved imaging, we observed that higher viral input leads to more rapid viral activity and notable changes in the organisation of nuclear material. As the infection progresses, the structural arrangement within the nucleus becomes increasingly altered, eventually compromising nuclear integrity in a manner that depends on the level of viral exposure.

Our observations suggest a dose-dependent relationship between viral input and nuclear architecture changes, with implications for how cells respond to and are impacted by infection. These findings underscore the significance of viral load in determining the cellular outcomes of HSV-1 infection and contribute to a better understanding of virus–host dynamics.}},
  author       = {{Cegielski, Blazej}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Uncovering Viral Dose–Driven Control of Herpesvirus DNA Replication and Infection-Induced Nuclear Damage}},
  year         = {{2025}},
}