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7.5.3 KSHV-Induced Immune Escape and Regulation
During KSHV infection, the host immune system recognizes various pathogen-
associated molecular patterns (PAMPs) of KSHV by pattern recognition receptors
(PRRs) to clear infection; however, KSHV has developed many ways to counteract
host immunosurveillance, which is critical for its survival and related disease pro-
gression. PRRs can be classified into four groups based on their localization and
function: free receptors in serum, membrane-bound phagocytic receptors,
membrane- bound signaling receptors, and cytoplasmic signaling receptors. Among
these, four types of PRRs have been extensively studied in the KSHV field: Toll-like
Fig. 7.3 Schematic representation of KSHV protein-induced angiogenesis-related signaling path-
way. The KSHV K1 protein induces VEGF expression, and secreted VEGF binds to VEGFR to
promote angiogenesis. K15 recruits and activates PLCγ1, which in turn activates downstream
NFAT1 to induce RCAN1/DSCR1 expression and capillary tube formation. vGPCR activates
JNK/SAPK, p38MAPK, and HIF-1α (which activates VEGF expression), which induce an angio-
genic phenotype in infected cells. vIL6 (ORF-K2) cooperates with vGPCR to upregulate angiopoi-
etin- 2 (Ang2) through the mitogen-activated protein kinase (MAPK) pathway. LANA promotes
angiogenesis in multiple phases: ( 1 ) LANA stabilizes Notch intracellular domain (ICN) and
induces Hey1; ( 2 ) LANA activates NF-κB and induces proangiogenic factor Ephrin-B2 expres-
sion; ( 3 ) LANA antagonizes the inhibitory activity of Ets-1/Daxx complexes on VEGF and induces
VEGF expression
7 KSHV Epidemiology and Molecular Biology