@article{3fcb781280454d76a0668a8a8e7bf93b,
title = "Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis",
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.",
keywords = "Autophagy, Beclin 2, Endolysosomal trafficking, Oncogenesis, Viral GPCR",
author = "Xiaonan Dong and Adam Cheng and Zhongju Zou and Yang, \{Yih Sheng\} and Sumpter, \{Rhea M.\} and Huang, \{Chou Long\} and Govind Bhagat and Virgin, \{Herbert W.\} and Lira, \{Sergio A.\} and Beth Levine",
note = "Funding Information: We thank Drs. Noelle Williams and Changguang Wang of the University of Texas Southwestern Preclinical Pharmacology Core for evaluating mouse plasma doxycycline levels (the Core is supported in part by the Institute for Innovations in Medical Technology); Drs. Gary S. Hayward (Johns Hopkins University School of Medicine), Nicholas Conrad (University of Texas Southwestern Medical Center), Jae U. Jung (Keck School of Medicine, University of Southern California), and Pinghui Feng (Keck School of Medicine, University of Southern California) for providing critical reagents; Haley Harrington for assistance with manuscript preparation; and Lori Nguyen for technical assistance. This work was supported by National Institutes of Health Grants R01 CA109618 (to B.L.), U19 AI109725 (to B.L. and H.W.V.), P01 DK072201 (to S.A.L.), and R01 CA161373 (to S.A.L.); the University of Texas Southwestern Medical Center O''Brien Center Grants P30 DK079328 (to C.-L.H.) and K08 AI099150 (to R.M.S.); Cancer Prevention Research Institute of Texas Grant RP120718 (to B.L.); and a Burroughs Wellcome Career Medical Scientist Award (to R.M.S.).",
year = "2016",
month = mar,
day = "15",
doi = "10.1073/pnas.1601860113",
language = "English",
volume = "113",
pages = "2994--2999",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "11",
}