Varicella-zoster virus DNA synthesis machinery

The Varicella-zoster virus (VZV) DNA synthesis machinery is a multi-protein assembly essential for the replication of the viral genome during the lytic phase of infection (PMID: 21543484). The central component of this machinery is the VZV DNA polymerase (encoded by ORF28), which catalyzes the addition of deoxynucleotides to the growing DNA strand (UniProt: P09252). This process is supported by auxiliary proteins, including the helicase-primase complex (ORF5, ORF6, and ORF52), which unwinds the DNA template, and the processivity factor (ORF16), which ensures the polymerase remains attached to the DNA (PMID: 21543484). This machinery is the primary target for most current anti-herpetic therapies used to treat chickenpox and shingles (herpes zoster). Nucleoside analogs like acyclovir and valacyclovir act as prodrugs that, upon activation by viral thymidine kinase, competitively inhibit the DNA polymerase and cause premature DNA chain termination (StatPearls: NBK542180). Newer therapeutic strategies include helicase-primase inhibitors like amenamevir, which offer a different mechanism of action and are effective against strains resistant to traditional polymerase inhibitors (PMID: 28838911). By disrupting the DNA synthesis machinery, these drugs effectively halt viral replication, thereby reducing the severity of clinical symptoms and the risk of complications like postherpetic neuralgia (PMID: 21543484).

Other names

Varicella-zoster virus DNA polymeraseVZV DNA replication complexORF28Helicase-primase complexVZV DNA synthesis machinery

Competitive inhibition of DNA polymerase and DNA chain termination; Pyrophosphate analog inhibition; Helicase-primase inhibition