This study reported for the first time that viral interferon regulatory factor 3 (vIRF3) is detected in over 40% of KS lesions and functioning as a proangiogenic factor, inducing hyper sprouting formation and abnormal growth of lymphatic endothelial cells in a histone deacetylase 5 (HDAC5) dependent manner, which is a signal-response regulator for vascular homeostasis [13]. Here, HDAC5 is linked to Kaposi's sarcoma.