Table 1.
Immune evasion strategies employed by HSV.
| Viral protein | Effect | Mechanism | References |
|---|---|---|---|
| Inhibition of IFN and cytokine signalling and IFN function | |||
| ICP0 | Enhanced resistance to IFN | Modification of IRF3 and IRF7 activation | [70–74] |
| ICP27 | Decreased IFN and cytokine expression | Reduces IRF3 and NF-κB activation | [27] |
| Us3 | Decreased ISG expression (Mx) and reduced IRF3 activation | n.d. | [79] |
| vhs | Inhibition of IFN-α/β production | Potentially because of reduced IRF7 activation | [80–82] |
| vhs | Inhibition of JAK/STAT signalling | Induction of SOCS3, repression of STAT1 activation | [82,83] |
| ICP27 | Inhibition of IFN signalling | Decreased STAT1 activation and translocation to the nucleus | [78] |
| vhs | Suppression of proinflammatory cytokines, IFNs, and chemokines | n.d. | [84] |
| ICP34.5 | Suppression of antiviral genes | Inhibition of IRF3 activation via interaction with TBK1 | [85] |
| ICP34.5 | Inhibition of PKR and PERK activity | Reverses the PKR and PERK-induced phosphorylation of eIF2α | [61,62,86] |
| Us11 | Inhibition of dsRNA-dependent and PACT-mediated activation of PKR | Binds to dsRNA | [63] |
| Binds to PKR | [64] | ||
| Us11 | Inhibition of 2′–5′ OAS | Binding to dsRNA (dsRNA binding domain of Us11 essential) | [67] |
| 2′–5′A analog | Inhibition of the 2′–5′ OAS/ RNAse L system | 2′–5′ A analogue | [69] |
| ICP0 | Inhibition of RNAseL-independent rRNA degradation | n.d. | [68] |
| Inhibition of host gene expression | |||
| ICP0 | Inhibition of TLR-induced JNK and NF-κB activation | Recruitment of USP7 binding to TRAF6 and IKKγ | [87] |
| ICP27 | Inhibition of splicing | Interacts with spliceosome components | [88–90] |
| ICP27 | Reduction of mRNA stability | n.d. | [91] |
| VP16 and vhs | RNA degradation | n.d. | [92] |
| ICP0 | Cell cycle arrest and disturbed cellular gene expression | Upregulation of p53-responsive genes. | [93] |
| Unknown | Inhibition of NFAT activation | n.d. | [94] |
| Inhibition of apoptosis | |||
| ICP4 | Inhibition of apoptosis | n.d. | [95] |
| gJ | Inhibition of apoptosis | Inhibition of caspase activation | [96] |
| ICP27 | Inhibition of apoptosis | n.d. | [97] |
| ICP34.5 | Inhibition of apoptosis | Inhibition of PKR activity | [62] |
| Inhibition of CTL-induced cell death (apoptosis) | Downregulation of cell surface Fas ligand | [98,99] | |
| Inhibition of autophagy and anti-microbial proteins | |||
| ICP0 and ICP0 | Inhibition of SLPI | n.d. | [100] |
| ICP34.5 | Inhibition of autophagy | Targeting of Beclin-1 | [66] |
| Inhibition of complement, antigen presentation and APC function | |||
| gC | Inhibition of complement | Binds to complement factor C3 | [101,102] |
| gE/gI complex | Blocking of Fc-mediated activities, including complement activation and ADCC | Binds to Fc domain of IgG | [103] |
| vhs | Inhibition of DC maturation and reduced cytokine production | n.d. | [104,105] |
| ICP47 | Inhibition of antigen presentation by MHC I | Interferes with TAP1/TAP2 | [106–108] |
| vhs | Inhibition of antigen presentation by MHC I and MHC II | Interferes with MHC I transport. Reduces levels of MHC II | [109–111] |
| gB | Inhibition of MHC II-mediated antigen presentation | Inhibited expression of invariant chain and interacts with HLA-DR and HLA-DM | [112] |
Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CTL, cytotoxic T lymphocyte; DC, dendritic cell; HLA, human leukocyte antigen; ICP, infected cell protein; JAK, janus kinase; MHC, major histocompability complex; n.d., not determined; NFAT, nuclear factor of activated T cell; PACT, PKR-activating protein; PERK, PKR-like endoplasmic-reticulum (ER)-resident kinase; PKR, dsRNA-activated protein kinase R; SLPI, secretory leukocyte protease inhibitor; SOCS, suppressor of cytokine signalling; STAT, signal transducer and activator of transcription; TAP, transporter accociated with antigen presentation; vhs, virion-host shutoff protein.