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. Author manuscript; available in PMC: 2020 Jul 28.
Published in final edited form as: Semin Cancer Biol. 2008 Oct 2;18(6):423–436. doi: 10.1016/j.semcancer.2008.09.003

Table 1.

KSHV modulation of the host immune system.

Responses ORF Gene product Celluar homolog Functions Mechanisms
Complement cascade ORF4 KCP RCA Blocks complement activation Enhances C3 convertase decay; prevents C3b deposition; factor I cofactor activity
IFN signaling K9 vIRF1 IRF Inhibits IRF3-mediated transcription; cell transformation P300/CBP sequestration; antagonizes p53, ATM, GRIM 19 activity and TGFβ signaling?
K11.1-K11 vIRF2 IRF Inhibits IRF3-mediated transcription
K10.5-K10.6 vIRF3 IRF Inhibits IRF7-mediated transcription Inhibition of IRF7 DNA binding
ORF50 RTA Inhibits IRF7 activation IRF7 ubiquitination and degradation
ORF45 Inhibits IRF7 activation Inhibition of IRF7 phosphorylation/nucleartranslocation
K8 K-bZIP Inhibits IRF3-mediated transcription Transcription repressor of IFN-β promoter
Chemokine Network K4 vCCL2 CC chemokine Th2 chemotaxis, angiogenesis CCR3 agonist; C-, CC-, CXC-, CX3C-R antagonist
K6 vCCL1 CC chemokine Th2 chemotaxis, angiogenesis CCR8 agonist
K4.1 vCCL3 CC chemokine Th2 chemotaxis, angiogenesis CCR4 agonist
ORF74 vGPCR GPCR Inflammation, angiogenesis; cell transformation Activates PI3K/AKT/mT0R pathway; activates NFkB, AP-1, HIF-1α trascriptional activities
K2 vIL6 IL6 Inflammation, angiogenesis IFNa-inducible; gp80-independent signaling; activates JAK/STAT and MAPK pathway
K12 Kaposin B Increases cytokines release Activates MK2, blocks cytokine mRNA decay
K14 vCD200 CD200 Suppress macrophage activity CD200R-mediated inhibitory signaling
Apoptosis and autophagy K13 vFLIP FLIP Anti-apoptosis, in cell transformation spindle shape, inflammation Blocks activation of caspase 8? NFκB pathway activation
ORF16 vBcl-2 Bcl-2 Anti-apoptosis, anti-autophagy Inhibits pro-apoptotic Bcl-2 family proteins; inhibits Beclin1-mediated autophagy
K7 vIAP IAP Anti-apoptosis, interferes with ubiquitin-proteasome pathway Inhibits caspase 3 and CAML activity; inhibits PLIC-regulated Ub-proteasome pathway
ORF73 LANA Cell growth transformation Inhibits p53, Rb, GSK-3β; and TGF-β pathways
ORF50 RTA Anti-apoptosis Inhibits p53 transcriptional activity
CTL and NK responses K3 vMIR1 MARCH CTL cell evasion Downregulation of HLA-A, -B, -C, and -E
K5 VMIR2 MARCH CTL and NK cell evasion Downregulation of HLA-A, -B, ICAM-1, B7–2, MICA/B, ALCL, CDld, PECAM, ALCAM and IFNγRI