Year: 2026
Type: dissertation
Abstract: Herpesviruses are widespread human pathogens that cause diseases ranging from mild mucocutaneous infections to severe encephalitis and malignancies.Among them, herpes simplex virus type 1 is a neurotropic virus that primarily infects epithelial cells and establishes lifelong latency in sensory neurons.Although the molecular biology of herpesvirus infection has been extensively studied, the physical mechanisms that govern capsid transport, genome release, and virus-host interactions at the nucleus remain incompletely understood.A critical step in HSV-1 infection is the transport of the DNA-filled capsid along microtubules to the nuclear periphery, where it docks at the nuclear pore complex through interactions between viral proteins and host nucleoporins.Docking is followed by ejection of the tightly confined viral genome into the nucleus, driven by the high internal pressure stored within the capsid.Once inside the nucleus, the viral genome either initiates lytic replication or persists as a latent episome.The molecular and mechanical factors that influence these outcomes remain unclear.This thesis examines HSV-1 infection from a biophysical perspective, with emphasis on the mechanical properties of the viral genome and the host nucleus during early stages of infection.Using small-angle neutron scattering, the structural organization of viral DNA within the capsid was investigated under conditions relevant to genome confinement and release.In parallel, the mechanical response of host nuclei following attachment of HSV-1 capsids was studied via fluorescence and scanning microscopy.By investigating these physical mechanisms, this work contributes to a deeper understanding of herpesvirus infection dynamics and may aid in the development of novel antivirals targeting the mechanical properties of viral genomes.
Author: Tsimtsirakis, Efthymios
Institution: Lund University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160672731