# Baculoviruses exploit the mitotic kinase CDK1 to disrupt the nuclear lamina

## TL;DR

Baculoviruses use the host's CDK1 kinase to disrupt the nuclear lamina, enabling efficient viral replication and nucleocapsid egress.

## Contribution

Baculoviruses are shown to exploit CDK1 to phosphorylate lamin B at S47, a novel mechanism for nuclear lamina disruption.

## Key findings

- Baculovirus infection triggers endogenous nuclear lamina disassembly via phosphorylation of lamin B at S47.
- CDK1 is directly used by baculoviruses to phosphorylate lamin B, enabling efficient viral nucleocapsid egress.
- Lamina disruption is essential for the production of infectious baculovirus particles.

## Abstract

The nuclear lamina is disassembled during mitosis, and certain DNA viruses exploit this process to facilitate replication. While we previously showed that baculoviruses disrupt the exogenously integrated lamina, their impact on the endogenous structure, the underlying mechanism, and the functional consequences for viral replication remained unknown. Here, we demonstrate that baculovirus infection triggers endogenous nuclear lamina disassembly, and that phosphorylation of lamin B at the N-terminal “mitotic site” serine 47 (S47) is the key event driving this process. Using in vitro phosphorylation assays, phospho-specific reagents, and site-directed mutagenesis, we further show that baculoviruses exploit the mitotic kinase cyclin-dependent kinase 1 (CDK1) to directly phosphorylate S47, thereby disrupting the lamina. Critically, this baculovirus-induced lamina disruption is not an epiphenomenon; transmission electron microscopy and viral titer assays demonstrate it is essential for the efficient nuclear egress of nucleocapsids and the production of infectious budded virions. Our study thus defines a distinct mechanism of viral subversion, wherein a virus directly repurposes the core mitotic machinery to breach the nuclear lamina barrier, a finding that significantly advances our understanding of host‒pathogen conflict.

The rigid meshwork of the nuclear lamina represents a natural barrier to the replication of many DNA viruses, particularly by impairing progeny nucleocapsid nuclear egress. Nevertheless, viruses are masters of trickery, manipulating the host cellular machinery to ensure efficient replication. Herpesviruses and circoviruses have developed ways to target the N-terminal “mitotic site”, a conserved phosphorylation site known to mediate lamina disassembly during mitosis, for lamin phosphorylation and subsequent lamina disruption. While baculovirus infection disrupts the exogenously integrated nuclear lamina, whether and how the endogenous nuclear lamina is affected remains to be elucidated. In the present study, we found that baculoviruses induce the disruption of the endogenous nuclear lamina, and this process is also mainly mediated by phosphorylation of the lamin N-terminal “mitotic site”. Intriguingly, unlike other previously studied viruses, baculoviruses exploit the mitotic kinase cyclin-dependent kinase 1 (CDK1) to phosphorylate lamin, disrupt the nuclear lamina, and permit nuclear egress. Baculovirus is the first virus discovered to exploit CDK1 for virus-induced lamina disruption, revealing a cunning strategy in which baculovirus breaches the nuclear lamina barrier in a distinct manner compared with other viruses and highlighting the diverse ways in which viruses overcome host barriers.