Skip to Main content Skip to Navigation
Journal articles

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.

Abstract : Latency-associated nuclear antigen 1 (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 the endothelial response to tumor necrosis factor alpha (TNF-α) stimulation and inhibits consequent neutrophil chemotaxis. Reporter assays showed that LANA-1 constantly repressed nuclear factor (NF)-κB transactivity upon TNF-α stimulation. We also found that LANA-1 decreased nuclear p65 protein levels through enhancement of polyubiquitylation-mediated p65 degradation and that an elongin B/elongin C-cullin 5-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 sheds light on a new mechanism by which KSHV during the latent life cycle evades the host innate immune response.
Document type :
Journal articles
Complete list of metadatas

Cited literature [102 references]  Display  Hide  Download

https://hal-riip.archives-ouvertes.fr/pasteur-00624240
Contributor : Xiaojing Lin <>
Submitted on : Friday, September 16, 2011 - 10:49:50 AM
Last modification on : Thursday, August 22, 2019 - 11:02:17 AM
Long-term archiving on: : Sunday, December 4, 2016 - 5:53:11 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Xiaofan Li, Deguang Liang, Xianzhi Lin, Erle S Robertson, Ke Lan. 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.. Journal of Virology, American Society for Microbiology, 2011, 85 (17), pp.8606-15. ⟨10.1128/JVI.00733-11⟩. ⟨pasteur-00624240⟩

Share

Metrics

Record views

156