Journal article
Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis
Proceedings of the National Academy of Sciences - PNAS, Vol.113(11), pp.2994-2999
03/15/2016
DOI: 10.1073/pnas.1601860113
PMCID: PMC4801257
PMID: 26929373
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.
Details
- Title: Subtitle
- Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis
- Creators
- Xiaonan Dong - The University of Texas Southwestern Medical CenterAdam Cheng - The University of Texas Southwestern Medical CenterZhongju Zou - The University of Texas Southwestern Medical CenterYih-Sheng Yang - The University of Texas Southwestern Medical CenterRhea M. Sumpter - The University of Texas Southwestern Medical CenterChou-Long Huang - The University of Texas Southwestern Medical CenterGovind Bhagat - NewYork–Presbyterian HospitalHerbert W. Virgin - Washington University in St. LouisSergio A. Lira - Icahn School of Medicine at Mount SinaiBeth Levine - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.113(11), pp.2994-2999
- Publisher
- Natl Acad Sciences
- DOI
- 10.1073/pnas.1601860113
- PMID
- 26929373
- PMCID
- PMC4801257
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Number of pages
- 6
- Grant note
- Burroughs Wellcome Career Medical Scientist Award R01CA109618 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) RP120718 / Cancer Prevention Research Institute of Texas Institute for Innovations in Medical Technology K08AI099150 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01 CA109618; U19 AI109725; P01 DK072201; R01 CA161373 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 DK079328; K08 AI099150 / University of Texas Southwestern Medical Center O'Brien Center P30DK079328 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 03/15/2016
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359589202771
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