Herpesviruses show consistency in their nuclear egress-associated induction of lamina-depleted areas as measured in an autofluorescent reporter cell model.
- 1Harald zur Hausen Institute of Virology, Friedrich-Alexander University of Erlangen- Nürnberg (FAU), Erlangen, Germany.
- 2La Jolla Institute for Immunology, San Diego, CA, USA.
- 3Harald zur Hausen Institute of Virology, Friedrich-Alexander University of Erlangen- Nürnberg (FAU), Erlangen, Germany. [email protected].
Abstract
Human herpesvirus infections span a wide variety of pathogenic outcomes, with individual representatives comprising a huge clinical relevance on human health. Translational research efforts are directed towards the improvement of broadly applicable preventive measures and detailed understanding of viral pathogenesis. Here, we studied rate-limiting steps in viral replication that show high mechanistic conservation among the Herpesviridae family members, in particular concerning the viral nucleocytoplasmic capsid egress. As characterized for several herpesviruses, viral nuclear egress is facilitated by the virus-induced local nuclear lamina rearrangements of infected cells. Hereby, the virus-mediated site-specific phosphorylation at lamin A/C Ser22, followed by cis/trans isomerization of the structural conformation, leads to the induction of lamina-depleted areas (LDAs). We have generated an LDA reporter system in primary human fibroblasts (HFFs), which conditionally express the autofluorescent lamin A/C-RFP fusion construct, for quantifying viral nuclear egress activity. This system was successfully applied for human and animal cytomegaloviruses as well as a selection of α-, β-, and γ-herpesviruses shown here. Our results illustrate that (i) the reporter system was effective in a quantitative way for all viruses analyzed; (ii) the process of LDA formation showed consistency among herpesviruses; (iii) the impairment of viral kinase activity, responsible for lamin A/C Ser22 phosphorylation, significantly reduced LDA formation; and (iv) inhibitory small molecules, directed either to the viral nuclear egress complex or the cellular isomerase activity, likewise provide an LDA-blocking effect leading to strong antiviral efficacy. Thus, the autofluorescent reporter cell model provides manifold options to study herpesviral productive replication, nuclear host interaction, and the pathogenesis-related impact of regulatory factors.
Related
- Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells
- Systemic Mastocytosis With Associated Acute Myeloid Leukemia Identified After Induction Therapy: A Case Report and Literature Review
- Antiviral Activity of an Ethanolic Extract of Cinnamomum cassia and Cinnamaldehyde Against the Herpesviruses HSV-1 and VZV
- Response to Venetoclax and Azacitidine in Induction-Refractory Adult Acute Myeloid Leukemia with UBTF Tandem Duplication and Associated Aberrant Splicing: A Case Report
- Med1 deletion reprograms dental epithelium into a hair-forming epidermal architecture associated with Trp63 induction.
BibTeX
@article{dhotre2026herpesviruses,
title = {{Herpesviruses show consistency in their nuclear egress-associated induction of lamina-depleted areas as measured in an autofluorescent reporter cell model.}},
author = {Kishore Dhotre and Lena Weghorn and Martin Schütz and Manfred Marschall},
journal = {Virology journal},
year = {2026},
month = oct,
doi = {10.1186/s12985-026-03334-8},
url = {https://europepmc.org/article/MED/42902406},
note = {CC BY},
}
RIS
TY - JOUR
TI - Herpesviruses show consistency in their nuclear egress-associated induction of lamina-depleted areas as measured in an autofluorescent reporter cell model.
AU - Kishore Dhotre
AU - Lena Weghorn
AU - Martin Schütz
AU - Manfred Marschall
PY - 2026
DA - 2026/10/20
JO - Virology journal
DO - 10.1186/s12985-026-03334-8
UR - https://europepmc.org/article/MED/42902406
AB - Human herpesvirus infections span a wide variety of pathogenic outcomes, with individual representatives comprising a huge clinical relevance on human health. Translational research efforts are directed towards the improvement of broadly applicable preventive measures and detailed understanding of viral pathogenesis. Here, we studied rate-limiting steps in viral replication that show high mechanistic conservation among the Herpesviridae family members, in particular concerning the viral nucleocytoplasmic capsid egress. As characterized for several herpesviruses, viral nuclear egress is facilitated by the virus-induced local nuclear lamina rearrangements of infected cells. Hereby, the virus-mediated site-specific phosphorylation at lamin A/C Ser22, followed by cis/trans isomerization of the structural conformation, leads to the induction of lamina-depleted areas (LDAs). We have generated an LDA reporter system in primary human fibroblasts (HFFs), which conditionally express the autofluorescent lamin A/C-RFP fusion construct, for quantifying viral nuclear egress activity. This system was successfully applied for human and animal cytomegaloviruses as well as a selection of α-, β-, and γ-herpesviruses shown here. Our results illustrate that (i) the reporter system was effective in a quantitative way for all viruses analyzed; (ii) the process of LDA formation showed consistency among herpesviruses; (iii) the impairment of viral kinase activity, responsible for lamin A/C Ser22 phosphorylation, significantly reduced LDA formation; and (iv) inhibitory small molecules, directed either to the viral nuclear egress complex or the cellular isomerase activity, likewise provide an LDA-blocking effect leading to strong antiviral efficacy. Thus, the autofluorescent reporter cell model provides manifold options to study herpesviral productive replication, nuclear host interaction, and the pathogenesis-related impact of regulatory factors.
SN - 1743-422X
ER -