Wolbachia blocks viral genome replication early in infection without a transcriptional response by the endosymbiont or host small RNA pathways

Rainey, S. M. et al. (2016) Wolbachia blocks viral genome replication early in infection without a transcriptional response by the endosymbiont or host small RNA pathways. PLoS Pathogens, 12(4), e1005536. (doi:10.1371/journal.ppat.1005536) (PMID:27089431) (PMCID:PMC4835223)

Rainey, S. M. et al. (2016) Wolbachia blocks viral genome replication early in infection without a transcriptional response by the endosymbiont or host small RNA pathways. PLoS Pathogens, 12(4), e1005536. (doi:10.1371/journal.ppat.1005536) (PMID:27089431) (PMCID:PMC4835223)

[img]
Preview
Text
119083.PDF - Published Version
Available under License Creative Commons Attribution.

2MB

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 mosquito-borne 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schnettler, Dr Esther and Varjak, Dr Margus and Rainey, Dr Stephanie and Mcdonald, Dr Melanie and Kohl, Professor Alain
Authors: Rainey, S. M., Martinez, J., McFarlane, M., Juneja, P., Sarkies, P., Lulla, A., Schnettler, E., Varjak, M., Merits, A., Miska, E. A., Jiggins, F. M., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7374
ISSN (Online):1553-7374
Published Online:18 April 2016
Copyright Holders:Copyright © 2016 Rainey et al.
First Published:First published in PLoS Pathogens 12(4): e1005536
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH