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.
Mo et al. (Thu,) studied this question.