Herpes simplex virus 1 UL52 primase (UL52)

The Herpes simplex virus 1 UL52 primase is the primase subunit of the heterotrimeric helicase-primase (HP) complex, alongside UL5 (helicase) and UL8 (auxiliary), essential for HSV-1 DNA replication. It synthesizes short RNA primers on single-stranded DNA templates at replication forks, enabling DNA polymerase to initiate leading and lagging strand synthesis, while exhibiting structural features like conserved catalytic motifs (I, II, III), a zinc-binding domain, and domains (NTD, MD, CTD) that scaffold complex assembly and DNA binding. UL52 binds ssDNA tails, coordinates with UL5 for 5'-3' translocation and duplex unwinding, and requires dimerization of the HP complex for full primase activity. In HSV-1 infection, it drives viral genome replication post-origin recognition by UL9 and ICP8, making the HP complex a validated antiviral target. Inhibitors like amenamevir and pritelivir bind the UL5-UL52 interface, blocking translocation and primer formation to halt replication. Cryo-EM structures reveal UL52's bilobed architecture stabilizing the complex, with mutations disrupting zinc binding or subunit interactions abolishing activity and viral propagation. Neither UL52 nor UL5 functions enzymatically alone, underscoring their interdependence.

Other names

HSV-1 primase subunitUL52 subunit of helicase-primase complex

Inhibition of helicase-primase complex activity, Disruption of viral DNA unwinding and primer synthesis