Related Experiment Video
Updated: Jan 10, 2026

Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Cytomegalovirus disrupts Lamin A/C to control microtubule-mediated nuclear movement and cell migration
Jamil Mahmud1, Ipsita Nandi1, Dean J Procter1
1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Abstract:
Human cytomegalovirus (HCMV) disrupts the inner nuclear Lamin A/C meshwork to facilitate virion egress. Here, we show that targeting Lamin A/C also plays a previously unrecognized role in HCMV-induced rewiring of cytoskeletal connections that control nuclear movement and cell migration at later stages of infection. Specifically, HCMV was found to employ distinct strategies to downregulate Lamin A/C and SUN2, which together regulate linker of nucleoskeleton and cytoskeleton (LINC) complexes that most often connect the nuclear membrane with cytoplasmic actin filaments. Unexpectedly, inhibition of the viral kinase, pUL97, or expression of nonphosphorylatable mutants of Lamin A/C failed to restore SUN2 expression or significant actin filament assembly. Moreover, exogenous reexpression of SUN2 also failed to restore actin filaments. Instead, restoration of SUN2 or Lamin A/C expression impaired the formation of acetylated microtubules in infected cells. Furthermore, inhibition of pUL97, expression of Lamin A/C mutants or depletion of the tubulin acetyl transferase, ATAT1, all impaired HCMV-induced nuclear movement and cell migration. Our findings reveal that HCMV uses multiple strategies to selectively downregulate Lamin A/C and SUN2 in order to prevent these proteins from interfering with the formation of acetylated microtubules that mediate nuclear movement and cell migration, revealing additional roles for Lamin A/C remodeling during infection and insights into how cells control cytoskeletal interactions with the nucleus.
Insights
Human cytomegalovirus (HCMV) manipulates Lamin A/C and SUN2 to control nuclear movement and cell migration. HCMV selectively downregulates these proteins to enable acetylated microtubules, crucial for cell migration during infection.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Human cytomegalovirus (HCMV) infection alters nuclear architecture.
- Lamin A/C and SUN2 are key components of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.
- LINC complexes connect the nuclear envelope to the cytoskeleton, influencing nuclear positioning and cell migration.
Purpose of the Study:
- To investigate the role of Lamin A/C and SUN2 in HCMV-induced nuclear movement and cell migration.
- To elucidate the mechanisms by which HCMV manipulates Lamin A/C and SUN2 during infection.
- To understand how HCMV controls cytoskeletal interactions with the nucleus.
Main Methods:
- Studied HCMV-infected cells.
- Investigated the expression levels of Lamin A/C and SUN2.
- Assessed the impact of viral kinase pUL97 inhibition and Lamin A/C mutants on protein expression and cytoskeletal organization.
- Examined the effects of SUN2 or Lamin A/C re-expression.
- Analyzed the role of acetylated microtubules in nuclear movement and cell migration.
- Depleted the tubulin acetyl transferase ATAT1.
Main Results:
- HCMV downregulates Lamin A/C and SUN2 to facilitate virion egress and later-stage nuclear-cytoskeletal rewiring.
- Inhibition of viral kinase pUL97 or expression of nonphosphorylatable Lamin A/C mutants did not restore SUN2 expression or actin assembly.
- Exogenous re-expression of SUN2 or Lamin A/C impaired acetylated microtubule formation.
- Inhibition of pUL97, Lamin A/C mutants, or ATAT1 depletion impaired HCMV-induced nuclear movement and cell migration.
Conclusions:
- HCMV employs multiple strategies to downregulate Lamin A/C and SUN2.
- These downregulations prevent interference with acetylated microtubule formation, which is essential for nuclear movement and cell migration.
- Reveals novel roles for Lamin A/C remodeling in HCMV infection and provides insights into nuclear-cytoskeletal control.
Related Concept Videos
Intracellular Movement of Viruses and Bacteria
Cytoskeletal Coordination in Cell Migration
Microtubule Instability
Microtubules in Cell Motility
Microtubule Associated Motor Proteins
Cancer Cell Migration through Invadopodia

