Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis

Xiaonan Dong, Adam Cheng, Zhongju Zou, Yih Sheng Yang, Rhea M. Sumpter, Chou Long Huang, Govind Bhagat, Herbert W. Virgin, Sergio A. Lira, Beth Levine

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The ubiquitin-proteasome system degrades viral oncoproteins and other microbial virulence factors; however, the role of endolysosomal degradation pathways in these processes is unclear. Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, and a constitutively active viral G protein-coupled receptor (vGPCR) contributes to the pathogenesis of KSHV-induced tumors. We report that a recently discovered autophagy-related protein, Beclin 2, interacts with KSHV GPCR, facilitates its endolysosomal degradation, and inhibits vGPCR-driven oncogenic signaling. Furthermore, monoallelic loss of Becn2 in mice accelerates the progression of vGPCR-induced lesions that resemble human Kaposi's sarcoma. Taken together, these findings indicate that Beclin 2 is a host antiviral molecule that protects against the pathogenic effects of KSHV GPCR by facilitating its endolysosomal degradation. More broadly, our data suggest a role for host endolysosomal trafficking pathways in regulating viral pathogenesis and oncogenic signaling.

Original languageEnglish (US)
Pages (from-to)2994-2999
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number11
DOIs
StatePublished - Mar 15 2016

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Human Herpesvirus 8
Viral Proteins
G-Protein-Coupled Receptors
Innate Immunity
Carcinogenesis
Kaposi's Sarcoma
Oncogene Proteins
Virulence Factors
Proteasome Endopeptidase Complex
Ubiquitin
Antiviral Agents
Neoplasms

Keywords

  • Autophagy
  • Beclin 2
  • Endolysosomal trafficking
  • Oncogenesis
  • Viral GPCR

ASJC Scopus subject areas

  • General

Cite this

Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis. / Dong, Xiaonan; Cheng, Adam; Zou, Zhongju; Yang, Yih Sheng; Sumpter, Rhea M.; Huang, Chou Long; Bhagat, Govind; Virgin, Herbert W.; Lira, Sergio A.; Levine, Beth.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 11, 15.03.2016, p. 2994-2999.

Research output: Contribution to journalArticle

Dong, Xiaonan ; Cheng, Adam ; Zou, Zhongju ; Yang, Yih Sheng ; Sumpter, Rhea M. ; Huang, Chou Long ; Bhagat, Govind ; Virgin, Herbert W. ; Lira, Sergio A. ; Levine, Beth. / Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 11. pp. 2994-2999.
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