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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Genome, Viral*/genetics; Drosophila melanogaster/*genetics ; RNA, Viral/*genetics ; Virus Replication/*physiology ; Wolbachia/*metabolism; Animals ; Cell Line ; Humans ; MicroRNAs/genetics ; RNA, Small Interfering/genetics ; Semliki forest virus ; Symbiosis ; Transcription, Genetic

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.

Erratum in: PLoS Pathog. 2016 May;12(5):e1005639. (PMID: 27159401)

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094664MA United Kingdom WT_ Wellcome Trust; MC_UU_12014 United Kingdom MRC_ Medical Research Council; MC_UP_1102/13 United Kingdom MRC_ Medical Research Council; MC_UU_12014/8 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MC_UP_A550_1031 United Kingdom MRC_ Medical Research Council; United Kingdom CRUK_ Cancer Research UK

0 (MicroRNAs)
0 (RNA, Small Interfering)
0 (RNA, Viral)

Date Created: 20160419 Date Completed: 20160824 Latest Revision: 20220129

20231215

PMC4835223

10.1371/journal.ppat.1005536

27089431