PMID- 24550300
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20230815
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 7
DP  - 2014 Feb 18
TI  - UVRAG is required for virus entry through combinatorial interaction with the 
      class C-Vps complex and SNAREs.
PG  - 2716-21
LID - 10.1073/pnas.1320629111 [doi]
AB  - Enveloped viruses exploit the endomembrane system to enter host cells. Through a 
      cascade of membrane-trafficking events, virus-bearing vesicles fuse with acidic 
      endosomes and/or lysosomes mediated by SNAREs triggering viral fusion. However, 
      the molecular mechanisms underlying this process remain elusive. Here, we found 
      that UV-radiation resistance-associated gene (UVRAG), an autophagic tumor 
      suppressor, is required for the entry of the prototypic negative-strand RNA 
      virus, including influenza A virus and vesicular stomatitis virus, by a mechanism 
      independent of IFN and autophagy. UVRAG mediates viral endocytic transport and 
      membrane penetration through interactions with the class C vacuolar protein 
      sorting (C-Vps) tethering complex and endosomal glutamine-containing SNAREs 
      [syntaxin 7 (STX7), STX8, and vesicle transport through t-SNARE homolog 1B 
      (Vti1b)], leading to the assembly of a fusogenic trans-SNARE complex involving 
      vesicle-associated membrane protein (VAMP8), but not VAMP7. Indeed, UVRAG 
      stimulates VAMP8 translocation to virus-bearing endosomes. Inhibition of VAMP8, 
      but not VAMP7, significantly reduces viral entry. Our data indicate that UVRAG, 
      in concert with C-Vps, regulates viral entry by assembling a specific fusogenic 
      SNARE complex. Thus, UVRAG governs downstream viral entry, highlighting an 
      important pathway capable of potential antiviral therapeutics.
FAU - Pirooz, Sara Dolatshahi
AU  - Pirooz SD
AD  - Department of Molecular Microbiology and Immunology, Keck School of Medicine, 
      University of Southern California, Los Angeles, CA 90033.
FAU - He, Shanshan
AU  - He S
FAU - Zhang, Tian
AU  - Zhang T
FAU - Zhang, Xiaowei
AU  - Zhang X
FAU - Zhao, Zhen
AU  - Zhao Z
FAU - Oh, Soohwan
AU  - Oh S
FAU - O'Connell, Douglas
AU  - O'Connell D
FAU - Khalilzadeh, Payam
AU  - Khalilzadeh P
FAU - Amini-Bavil-Olyaee, Samad
AU  - Amini-Bavil-Olyaee S
FAU - Farzan, Michael
AU  - Farzan M
FAU - Liang, Chengyu
AU  - Liang C
LA  - eng
GR  - R01 CA140964/CA/NCI NIH HHS/United States
GR  - R21 CA161436/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140203
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (R-SNARE Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (UVRAG protein, human)
RN  - 0 (VAMP8 protein, human)
RN  - 0 (Vesicular Transport Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western
MH  - Chlorocebus aethiops
MH  - Cricetinae
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Green Fluorescent Proteins/metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Influenza A virus/physiology
MH  - Mice
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - NIH 3T3 Cells
MH  - Plasmids/genetics
MH  - R-SNARE Proteins/*metabolism
MH  - RNA Interference
MH  - RNA Viruses/*physiology
MH  - RNA, Small Interfering/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Tumor Suppressor Proteins/*metabolism
MH  - Vero Cells
MH  - Vesicular Transport Proteins/*metabolism
MH  - Vesiculovirus/physiology
MH  - *Virus Internalization
PMC - PMC3932887
OTO - NOTNLM
OT  - VSV
OT  - endocytic trafficking
OT  - influenza virus
COIS- The authors declare no conflict of interest.
EDAT- 2014/02/20 06:00
MHDA- 2014/04/16 06:00
PMCR- 2014/08/18
CRDT- 2014/02/20 06:00
PHST- 2014/02/20 06:00 [entrez]
PHST- 2014/02/20 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
PHST- 2014/08/18 00:00 [pmc-release]
AID - 1320629111 [pii]
AID - 201320629 [pii]
AID - 10.1073/pnas.1320629111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2716-21. doi: 
      10.1073/pnas.1320629111. Epub 2014 Feb 3.