Ribonucleotide reductase large subunit (ICP6) (ICP6)

The HSV-1 UL39 gene encodes the large subunit of the viral ribonucleotide reductase (RR), commonly known as Infected Cell Protein 6 (ICP6) [1]. This enzyme is essential for viral replication, particularly in non-dividing cells, as it catalyzes the conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, providing the necessary building blocks for DNA synthesis [2]. Beyond its metabolic function, ICP6 acts as a scaffold and signaling molecule that inhibits host cell death pathways, such as apoptosis and necroptosis, thereby promoting viral survival and pathogenesis [3]. Due to its critical role in the viral life cycle, UL39 has been targeted by experimental peptidomimetic inhibitors and thiosemicarbazones designed to disrupt the assembly of the RR holoenzyme [4]. Furthermore, the UL39 gene is frequently deleted in the engineering of oncolytic herpes simplex viruses (oHSVs) to restrict viral replication to neoplastic cells, which naturally possess high levels of endogenous ribonucleotide reductase [5]. This dual role as both a metabolic enzyme and an immune modulator makes UL39 a significant focus for both antiviral drug discovery and cancer virotherapy. [1] UniProt P06487; [2] Goldstein & Weller (1988) J. Virol.; [3] Dufour et al. (2011) J. Gen. Virol.; [4] Liuzzi et al. (1994) Nature; [5] Mineta et al. (1994) Nature Medicine.

Other names

UL39Ribonucleotide reductase 1R1Infected cell protein 6HSV-1 UL39 proteinRR1

Inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates, thereby depleting the dNTP pool required for viral DNA replication; or targeted deletion in oncolytic viruses to restrict replication to cells with high endogenous dNTP levels.