KSHV vIRF3 promotes angiogenesis of lymphatic endothelial cells (LECs)

Herein, we report viral interferon regulatory factor 3 (vIRF3) as a pro-angiogenic factor together with HDAC5 that coordinates with LEC transcriptome, thus resulting in hyper-sprouting formation and ultimately leading to abnormal lymphangiogenesis. Overexpression of vIRF3 in LECs but not blood endothelial cells (BECs) exhibited a unique KSHV-associated angiogenic effect, evidenced by elongated spindle shape, sprouting, and tube formation. Furthermore, using vIRF3 knockout recombinant KSHV, we confirmed that vIRF3 is a critical factor of KSHV-mediated lymphangiogenesis in primary LECs. Overall design: 3 control, 3 overexpressor each in LECs and BECs.