PMID- 29494679
OWN - NLM
STAT- MEDLINE
DCOM- 20180626
LR  - 20210109
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 14
IP  - 3
DP  - 2018 Mar
TI  - Wolbachia-mediated virus blocking in mosquito cells is dependent on XRN1-mediated 
      viral RNA degradation and influenced by viral replication rate.
PG  - e1006879
LID - 10.1371/journal.ppat.1006879 [doi]
LID - e1006879
AB  - Wolbachia is currently being developed as a novel tool to block the transmission 
      of dengue viruses (DENV) by Aedes aegypti. A number of mechanisms have been 
      proposed to explain the DENV-blocking phenotype in mosquitoes, including 
      competition for fatty acids like cholesterol, manipulation of host miRNAs and 
      upregulation of innate immune pathways in the mosquito. We examined the various 
      stages in the DENV infection process to better understand the mechanism of 
      Wolbachia-mediated virus blocking (WMVB). Our results suggest that infection with 
      Wolbachia does not inhibit DENV binding or cell entry, but reduces virus 
      replication. In contrast to a previous report, we also observed a similar 
      reduction in replication of West Nile virus (WNV). This reduced replication is 
      associated with rapid viral RNA degradation in the cytoplasm. We didn't find a 
      role for host miRNAs in WMVB. Further analysis showed that the 3' end of the 
      virus subgenomic RNA was protected and accumulated over time suggesting that the 
      degradation is XRN1-mediated. We also found that sub genomic flavivirus RNA 
      accumulation inactivated XRN1 in mosquito cells in the absence of Wolbachia and 
      led to enhancement of RNA degradation in its presence. Depletion of XRN1 
      decreased WMVB which was associated with a significant increase in DENV RNA. We 
      also observed that WMVB is influenced by virus MOI and rate of virus replication. 
      A comparatively elevated blocking was observed for slowly replicating DENV, 
      compared to WNV. Similar results were obtained while analysing different DENV 
      serotypes.
FAU - Thomas, Saijo
AU  - Thomas S
AUID- ORCID: 0000-0002-3730-3588
AD  - Institute of Vector-Borne Disease (IVBD), Monash University, Clayton, VIC, 
      AUSTRALIA.
FAU - Verma, Jiyoti
AU  - Verma J
AD  - Infection and Immunity Program, Biomedicine Discovery Institute and the 
      Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      VIC, AUSTRALIA.
FAU - Woolfit, Megan
AU  - Woolfit M
AD  - Institute of Vector-Borne Disease (IVBD), Monash University, Clayton, VIC, 
      AUSTRALIA.
FAU - O'Neill, Scott L
AU  - O'Neill SL
AD  - Institute of Vector-Borne Disease (IVBD), Monash University, Clayton, VIC, 
      AUSTRALIA.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180301
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (MicroRNAs)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Viral)
RN  - EC 3.1.- (Exoribonucleases)
RN  - EC 3.1.13.1 (XRN1 protein, human)
SB  - IM
MH  - Aedes/*immunology/metabolism/microbiology/virology
MH  - Animals
MH  - Dengue/immunology/*prevention & control/virology
MH  - Dengue Virus/physiology
MH  - Exoribonucleases/genetics/*metabolism
MH  - Humans
MH  - Insect Vectors/immunology/microbiology/virology
MH  - MicroRNAs
MH  - Microtubule-Associated Proteins/genetics/*metabolism
MH  - RNA, Viral/genetics/*metabolism
MH  - Symbiosis
MH  - *Virus Replication
MH  - West Nile Fever/immunology/*prevention & control/virology
MH  - West Nile virus/physiology
MH  - Wolbachia/*physiology
PMC - PMC5833283
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/03/02 06:00
MHDA- 2018/06/27 06:00
PMCR- 2018/03/01
CRDT- 2018/03/02 06:00
PHST- 2018/01/11 00:00 [received]
PHST- 2018/01/15 00:00 [accepted]
PHST- 2018/03/02 06:00 [entrez]
PHST- 2018/03/02 06:00 [pubmed]
PHST- 2018/06/27 06:00 [medline]
PHST- 2018/03/01 00:00 [pmc-release]
AID - PPATHOGENS-D-18-00065 [pii]
AID - 10.1371/journal.ppat.1006879 [doi]
PST - epublish
SO  - PLoS Pathog. 2018 Mar 1;14(3):e1006879. doi: 10.1371/journal.ppat.1006879. 
      eCollection 2018 Mar.