Table 1 Immune evasion genes of HSV
Gene | Protein | Function | oHSV name |
|---|---|---|---|
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. Down-regulation of MHC II processing pathway in CD4+ cells. | R5141; KNE |
UL44 | gC | Forms the initial attachment of the virus to the cell by binding to heparan sulfate. Inactivates serum complement proteins. | R5141 |
US6 | gD | Binds to HVeM and/or nectin-1, leading to a conformation change that initiates fusion. Down-regulates NK receptor ligand and NK-mediated lysis; inhibition of apoptosis. | R5141; R-LM249; HSV1716EGFR; KNE |
RL1 | ICP34.5 | Major neurovirulence gene. Suppression of PKR/eIF-2a signaling pathway and IFN-induced anti-viral mechanisms; Inhibits DC maturation and antigen. Presentation; Blocks MHC class II accumulation on the cell surface; Binds to Beclin-1, inhibiting autophagy. | HSV1716; R3616; OncoVexGMCSF; G47; ΔG207; DM33; |
RL2 | ICP0 | Blocks NF-κB-mediated transcription of immunomodulatory cytokines, and IRF3-induced and IRF7-induced anti-viral signaling pathways; inhibits IRF3 translocation to the nucleus; inhibits IFI16; degradation of mature DC marker (CD83). Involved in transcription of viral genes. Has ubiquitin ligase activity. Inhibits interferon response. Alters the cellular environment to promote viral replication. | R7020 (NV1020); |
UL39 | ICP6 | Major subunit of ribonucleotide reductase. Blocks TNF-a-mediated and Fas ligand-mediated apoptosis through interacting with caspase 8 and necroptosis. | hrR3; G47Δ |
UL54 | ICP27 | Inhibits cellular mRNA splicing. Recruits necessary proteins involved in viral transcription and translation. Activates cellular pathways to promote viral replication. Blocks NF-κB and IRF3 signaling pathways; blocks STAT1 activation and its translocation to the nucleus. | HF10 |
US12 | ICP47 | Down-regulates MHC class I by inhibiting TAP. | G47Δ; OncoVexGMCSF |
US11 | US11 | Binds to and is phosphorylated by PKR, preventing cellular inhibition of protein synthesis and autophagy; blocks OAS. | G47Δ |
US3 | US3 | Inhibits NF-κB activation and reduces cytokine expression, such as IL-8; inhibits induction of apoptosis; hyperphosphorylates IRF3 to block activation of RLR signaling pathway. | R7041 |
UL48 | VP16 | Initiates transcription of immediate early genes. Inhibits NF-κB activation and blocks IRF3 pathway and IFN-β production. | KM100 |