Host-directed clearance of nuclear tegument U14 terminates NF-κB signaling and supports HHV-6A replication.

U14 protein and PDLIM2 regulate NF-κB signaling termination, enabling productive HHV-6A infection, with U14 promoting viral replication through host interactions.

• Why it matters: Controlling immune responses during herpesvirus infection is crucial to prevent host damage while allowing virus replication. Understanding how NF-κB signaling is terminated can reveal targets for antiviral strategies.
• What they did: The study used CRISPR interference to manipulate PDLIM2 and U14 levels, examining their effects on NF-κB signaling, nuclear stress, and viral replication in HHV-6A-infected cells.
• The result: Findings show that the U14-PDLIM2 axis terminates NF-κB signaling and nuclear stress, facilitating viral gene expression and replication, highlighting a host-controlled mechanism supporting infection.