Table 1.
Summary of viral genes modified in oHSVs
| Gene | Protein | Function | Reference |
|---|---|---|---|
| RL1 | ICP34.5 | Major neurovirulence gene. Prevents cellular inhibition of protein synthesis by mediating dephosphorylation of eIF2α. Binds to Beclin-1, inhibiting autophagy. | 19 |
| RL2 | ICP0 | Multifunctional. Involved in transcription of viral genes. Has ubiquitin ligase activity. Inhibits interferon response. Alters the cellular environment to promote viral replication. |
45 |
| RS1 | ICP4 | Represses expression of viral immediate early genes and activates expression of viral early and late genes. | 53 |
| UL2 | Uracil DNA glycosylase | Removes uracil from DNA. | 36 |
| UL22 | gH | Binds to integrins. With gL and gB, enables fusion of the envelope with the cell membrane. | 69 |
| UL23 | Thymidine kinase | Involved in the synthesis of deoxyribonucleotide thymidine triphosphate. | 16 |
| UL27 | gB | Part of initial attachment of the virus to the cell by binding to heparan sulfate. With gH/gL, enables fusion of the envelope with the cell membrane. |
69 |
| UL39 | ICP6 | Major subunit of ribonucleotide reductase. | 18 |
| UL44 | gC | Forms the initial attachment of the virus to the cell by binding to heparan sulfate. | 69 |
| UL48 | pUL48/VP16 | Initiates transcription of immediate early genes. | 43 |
| UL53 | gK | Essential for cytoplasmic envelopment, egress, and cell fusion. | 32 |
| UL54 | ICP27 | Multifunctional. Inhibits cellular mRNA splicing. Recruits necessary proteins involved in viral transcription and translation. Activates cellular pathways to promote viral replication. | 62 |
| UL55 | pUL55 | Tegument protein. Function unknown. | 26 |
| UL56 | pUL56 | Binds to neuron-specific kinesin KIF1A, an axonal transport motor protein. | 28 |
| US6 | gD | Binds to HVEM and/or nectin-1, leading to a conformation change that initiates fusion. | 69 |
| US11 | pUS11 | Binds to and is phosphorylated by PKR, preventing cellular inhibition of protein synthesis and autophagy. | 41 |
| US12 | ICP47 | Inhibits TAP/MHC class I presentation. | 77 |
Abbreviations: eIF2α, elongation initiation factor 2α; g, glycoprotein; HVEM, herpesvirus entry mediator; ICP, infected cell protein; MHC, major histocompatibility complex; oHSV, oncolytic herpes simplex virus; p, protein; PKR, protein kinase R; RL, repeat long; RS, repeat short; TAP, transporter associated with antigen processing; UL, unique long; US, unique short; VP, viral protein.