Table 1.
Gammaherpesvirus innate immune evasion proteins and microRNAs
| Protein | Description | Evasion function |
|---|---|---|
|
| ||
| KSHV | ||
| ORF45 | Immediate-early tegument protein | Inhibits IRF7; negatively regulates cGAS-STING |
| K-bZIP (K8) | Late nuclear protein | Binds to IFN-β promoter and inhibits IRF3 activity |
| RIF (ORF10) | Late protein | Inhibits type I IFN production |
| ORF64 | Large tegument protein | Decreases RIG-I ubiquitination |
| LANA (ORF73) | Latency regulator | Decreases IFN-β production; negatively regulates cGAS-STING |
| RTA (ORF50) | Lytic transactivator | Lowers MyD88 expression; inhibits IRF7 expression; decreases TRIF stability and TLR3 signaling |
| ORF52 | Late tegument protein | Inhibits cGAS; inhibits IRF3 activation |
| ORF54 | Viral dUTPase | Inhibits type I IFN activity |
| vIRF1 | Homologous to cellular IRFs | Decreases IRF3 activity; inhibits MAVS; inhibits TLR3 signaling; negatively regulates cGAS-STING |
| vIRF2 | Homologous to cellular IRFs | Inhibits IRF1 and IRF3; inhibits TLR3 signaling |
| vIRF3 | Homologous to cellular IRFs | Inhibits IRF7; inhibits TLR3 signaling |
| vIRF4 | Homologous to cellular IRFs | Prevents IRF7 dimerization |
| ORF63 | Homologous to cellular NLRP1 | Inhibits inflammasome activity |
| vIL-6 | Homologous to cellular IL-6 | Blocks anti-proliferative effects of IFN signaling |
| ORF36 | Viral protein kinase | Negatively regulates cGAS-STING; inhibits IFN-β activity |
| miR-K9 | Viral microRNA | Inhibits IRAK1 and MyD88 |
| miR-K5 | Viral microRNA | Inhibits MyD88 |
| EBV | ||
| BGLF5 | Exonuclease | Downregulates TLR9 |
| BARF1 | Oncoprotein | Reduces IFN-α production |
| EBNA1 | Latent and lytic protein involved in viral genomic maintenance | Inhibits NF-κB signaling |
| BGLF2 | Tegument protein | Decreases phosphorylation of NF-κB subunits |
| BPLF1 | Large tegument protein; deubiquitinase | Downregulates TLR signaling; deubiquitinates TRAF6 |
| BZLF1 (ZTA) | Lytic transactivator | Inhibits IRF7; activates SOCS proteins |
| BRLF1 (RTA) | Lytic transactivator | Downregulates IRF3 and IRF7; decreases IFN-β levels |
| BILF4 (LF2) | Tegument protein | Prevents IRF7 dimerization |
| BFRF1 | Early protein | Inhibits IRF3 and production of IFN-β |
| LMP-1 | Latent membrane oncoprotein | Downregulates TLR9; reduces Tyk2 and STAT2 phosphorylation |
| LMP-2 | Latent membrane oncoprotein | Decreases STAT3 activation; reduces STAT1, JAK, and Tyk2 phosphorylation; degrades intracellular IFNAR |
| BHRF1 | Anti-apoptotic protein | Induces fission of mitochondria and degradation of MAVS |
| BGLF4 | Viral protein kinase | Inhibits IRF3; reduces STAT1 phosphorylation; decreases NF-κB signaling |
| miR-BART15 | Viral microRNA | Decreases NLRP3 expression |
| miR-BART16 | Viral microRNA | Inhibits IFN-α signaling and ISG production |
| miR-BART6-3p | Viral microRNA | Downregulates RIG-I and IFN-β |
| MHV68 | ||
| ORF36 | Viral protein kinase | Inhibits transcription of IFN-β |
| ORF64 | Large tegument protein | Inhibits IFN signaling |
| ORF54 | Viral dUTPase | Inhibits type I IFN activity; decreases expression of IFNAR |
| RTA (ORF50) | Lytic transactivator | Ubiquitinates NF-κB subunits, resulting in their degradation |
| ORF11 | Late protein | Prevents the interaction of TBK1 and IRF3 |