Herpes simplex virus DNA polymerase UL42–UL30 protein-protein interface (UL42–UL30 interface)

The **UL42/UL30 protein-protein interface** refers to the molecular interaction between the **UL42 processivity factor** and the **UL30 DNA polymerase catalytic subunit** of herpes simplex virus type 1. UL30 provides DNA polymerase and exonuclease activities, while UL42 enhances processivity by binding both UL30 (primarily via its C-terminus) and DNA. The interaction occurs through a flexible contact region, mainly at UL30’s C-terminal segment and a connector loop within UL42, involving salt bridges and positively charged surfaces that tether DNA and promote long-chain synthesis. Disruption of this interface prevents the formation of a fully processive viral polymerase, critically impairing viral DNA replication and replication origin usage. Structural studies reveal that UL42 is a monomer with a classic family B polymerase fold and that it mediates nuclear import of the holoenzyme via a bipartite nuclear localization signal (NLS). Targeting the UL42–UL30 interface is considered a promising antiviral strategy to inhibit HSV infections, and its specificity for the viral complex presents a lower risk of host toxicity

Other names

HSV polymerase accessory-catalytic interfaceHSV-1 DNA polymerase–processivity factor interaction

Potential interface inhibitors would block the physical association between UL42 and UL30, preventing formation of a processive viral DNA polymerase holoenzyme and thereby inhibiting viral replication