Herpes simplex virus 1 UL5 helicase-primase subunit (UL5)

The Herpes simplex virus 1 UL5 helicase-primase subunit (UL5) is a key component of the viral helicase-primase complex, alongside UL52 (primase) and UL8 (non-catalytic subunit), essential for unwinding duplex DNA at the replication fork during HSV-1 genome replication. As a superfamily 1 (SF1) helicase, UL5 translocates along single-stranded DNA in a 3' to 5' direction using ATP or GTP hydrolysis, featuring seven conserved motifs that form a four-domain structure (1A, 1B, 2A, 2B) with a central DNA-binding channel and a pin domain for duplex separation. It forms a stable heterotrimeric complex where UL5 interacts directly with UL52's N-terminus and UL8 coordinates activities, enabling primase to synthesize RNA primers for DNA polymerase (UL30). UL5 is critical for viral DNA synthesis, as mutations in its conserved motifs abolish replication function while preserving protein-protein interactions. In HSV-1 infection, the complex is recruited post-origin binding by UL9, supporting leading- and lagging-strand synthesis aided by ICP8. UL5 is a therapeutic target for antivirals like amenamevir and other HPIs, which bind to inhibit conformational changes needed for translocation and unwinding. Cryo-EM structures reveal its bilobed architecture and specific inhibitor binding sites at the UL5-UL52 interface, guiding drug development against herpesvirus replication.

Other names

UL5 gene productHSV-1 helicase subunit

Inhibition of helicase activity, Inhibition of DNA unwinding, Blockade of domain movements in SF1 helicase core