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Table 1 Immune evasion genes of HSV

From: Oncolytic herpes simplex virus and immunotherapy

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