Altmetric

Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways

File Description SizeFormat 
journal.ppat.1005536.PDFPublished version2.14 MBAdobe PDFView/Open
Title: Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways
Authors: Rainey, SM
Martinez, J
McFarlane, M
Juneja, P
Sarkies, P
Lulla, A
Schnettler, E
Varjak, M
Merits, A
Miska, EA
Jiggins, FM
Kohl, A
Item Type: Journal Article
Abstract: The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquitoborne Semliki Forest virus (SFV; Togaviridae, Alphavirus). Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3´ open reading frame than the 5´ non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia’s antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs) have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to an induced) mechanism.
Issue Date: 18-Apr-2016
Date of Acceptance: 23-Mar-2016
URI: http://hdl.handle.net/10044/1/32710
DOI: https://dx.doi.org/10.1371/journal.ppat.1005536
ISSN: 1553-7374
Publisher: Public Library of Science
Journal / Book Title: Plos Pathogens
Volume: 12
Issue: 4
Copyright Statement: © 2016 Rainey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Medical Research Council
Funder's Grant Number: MC-A652-5PZ80-3203-0000-0000
Keywords: Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: e1005536
Appears in Collections:Clinical Sciences
Molecular Sciences



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons