西亚试剂：Kaposi's sarcoma-associated herpesvirus-encoded latency-ass

Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen reduces interleukin-8 expression in endothelial cells and impairs neutrophil chemotaxis by degrading nuclear p65

Xiaofan Li, Deguang Liang, Xianzhi Lin, Erle S. Robertson, and Ke Lan

Latency-associated nuclear antigen (LANA)-1 of Kaposi's sarcoma-associated herpesvirus (KSHV) is the major viral latent protein and functions as a multifaceted protein. Here, we report that LANA-1 attenuates endothelial response to tumor necrosis factor (TNF)-α stimulation and inhibits consequent neutrophil chemotaxis. Reporter assay showed that LANA-1 constantly repressed nuclear factor (NF)-B transactivity upon TNF-α stimulation. We also found that LANA-1 decreased nuclear p65 protein level through enhancement of poly-ubiquitylation-mediated p65 degradation, and an ElonginB/C-Cullin5-LANA-1-p65 complex assembled by LANA-1 was responsible for this enhanced p65 degradation. In telomerase-immortalized human umbilical vein endothelial cells, LANA-1 was demonstrated to repress interleukin-8 expression, which was involved in neutrophil recruitment to the inflammatory site. Through an in vitro transmigration assay, we determined a suppressive effect of LANA-1 on neutrophil chemotaxis. Our work suggests that KSHV LANA-1 is a negative modulator of acute inflammation, and shed light on a new mechanism by which latently infected KSHV evades the host innate immune response.