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KSHV ORF57, a Protein of Many Faces
Open AccessArticle

Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity

by Hui Wu 1,†, Liqun Liu 2,†, Jun Xiao 1, Mengdie Chi 1, Yixiao Qu 1 and Hao Feng 1,*
1
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China
2
Division of Pediatric Neurology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha 410011, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Zhi-Ming Zheng
Viruses 2015, 7(4), 1627-1641; https://doi.org/10.3390/v7041627
Received: 24 October 2014 / Revised: 6 January 2015 / Accepted: 20 March 2015 / Published: 31 March 2015
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus)
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi’s Sarcoma (KS). KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling. View Full-Text
Keywords: KSHV; vGPCR; Glycosylation KSHV; vGPCR; Glycosylation
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MDPI and ACS Style

Wu, H.; Liu, L.; Xiao, J.; Chi, M.; Qu, Y.; Feng, H. Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity. Viruses 2015, 7, 1627-1641.

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