Impact of cellular structures on nuclear egress of herpesvirus capsids
Main funder
Funder's project number: 6420-1252f
Funds granted by main funder (€)
- 726 000,00
Funding program
Project timetable
Project start date: 01/01/2023
Project end date: 31/12/2025
Summary
The intranuclear assembly of progeny nucleocapsids and their subsequent nuclear egress are critical steps in the life cycle of most DNA viruses. Despite the fact that herpesviruses are a significant cause of various human diseases, and increasingly used in oncolytic virus therapy, their interactions and dynamics within the host cell nucleus remain poorly understood.
Mitochondria take central stage in cellular metabolism and herpesviruses are able to redirect host cell metabolism. After nuclear assembly of progeny viruses in the viral replication compartment is followed by their transportation through chromatin towards the nuclear envelope – their site of nuclear egress. We will determine how the structure and function of mitochondria and architecture of chromatin change during infection. Then we analyze how these changes in turn affects the intranuclear transport and nuclear egress of viral capsids. These studies are essential for understanding the viral spread, which is specifically required for oncolytic cancer therapy. This project is a part of our long-term studies elucidating the mechanisms of virus-induced change in host chromatin and the nuclear egress of progeny viruses.
Our research seeks to advance the knowledge of viral nuclear dynamics and interactions by employing a new interdisciplinary approach combining biology and biophysics with state-of-the-art techniques of imaging and advanced image analyses. Specific research questions are:
• How does infection affect structure and function of mitochondria?
• How do herpesviruses manipulate host chromatin organization?
• How does changes in host chromatin and mitochondria influence the nuclear mobility of viral capsids?
Mitochondria take central stage in cellular metabolism and herpesviruses are able to redirect host cell metabolism. After nuclear assembly of progeny viruses in the viral replication compartment is followed by their transportation through chromatin towards the nuclear envelope – their site of nuclear egress. We will determine how the structure and function of mitochondria and architecture of chromatin change during infection. Then we analyze how these changes in turn affects the intranuclear transport and nuclear egress of viral capsids. These studies are essential for understanding the viral spread, which is specifically required for oncolytic cancer therapy. This project is a part of our long-term studies elucidating the mechanisms of virus-induced change in host chromatin and the nuclear egress of progeny viruses.
Our research seeks to advance the knowledge of viral nuclear dynamics and interactions by employing a new interdisciplinary approach combining biology and biophysics with state-of-the-art techniques of imaging and advanced image analyses. Specific research questions are:
• How does infection affect structure and function of mitochondria?
• How do herpesviruses manipulate host chromatin organization?
• How does changes in host chromatin and mitochondria influence the nuclear mobility of viral capsids?
