Intranuclear HSV-1 DNA ejection induces major mechanical transformations suggesting mechanoprotection of nucleus
Alex Evilevitch1, Sophia V Hohlbauch2
1Department of Experimental Medical Science, Lund University, Lund 22184, Sweden; Alex.Evilevitch@med.lu.se.
Herpes simplex virus type 1 (HSV-1) infection initially stiffens chromatin and softens the nuclear lamina. This mechanical adaptation protects nuclear integrity during viral DNA ejection and replication.
Area of Science:
- Cellular mechanics
- Virology
- Nuclear biology
Background:
- Nuclear integrity is crucial for cell survival under mechanical stress.
- Herpesviruses cause mechanical strain on the nuclear envelope during replication and assembly.
- The initial mechanical effects of herpesvirus infection on the nucleus were previously unknown.
Purpose of the Study:
- To investigate the mechanical changes in the nucleus immediately after herpes simplex virus type 1 (HSV-1) DNA ejection.
- To understand how nuclear integrity is maintained during the early stages of HSV-1 infection.
Main Methods:
- Utilized an atomic force microscopy force volume mapping approach.
- Studied cell-free reconstituted nuclei with docked HSV-1 capsids.
- Analyzed the mechanical response of the nuclear lamina and chromatin to intranuclear DNA ejection.
Main Results:
- Chromatin stiffness (Young's modulus) increased approximately 14-fold.
- The nuclear lamina exhibited softening (increased elasticity).
- These changes occurred immediately following intranuclear HSV-1 DNA ejection.
Conclusions:
- Chromatin stiffening and lamina softening represent a mechanoprotective mechanism.
- Stiffened chromatin maintains nuclear morphology.
- Lamina softening acts as a shock absorber, preventing nuclear membrane rupture and facilitating viral genome replication.
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