Evidence of differences in cellular regulation of Wolbachia-mediated viral inhibition between alphaviruses and flaviviruses

Rainey, S. M., Lefteri, D. A. , Darby, C., Kohl, A. , Merits, A. and Sinkins, S. P. (2024) Evidence of differences in cellular regulation of Wolbachia-mediated viral inhibition between alphaviruses and flaviviruses. Viruses, 16(1), 115. (doi: 10.3390/v16010115) (PMID:38257815) (PMCID:PMC10818798)

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The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o’nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses.

Item Type:Articles
Additional Information:This research was funded by Wellcome Trust (202888, 108508) to S.P.S., and Wellcome Trust grant WT094664MA and Medical Research Council (MC_UU_12014/8, MC_UU_00034/4) awarded to A.K.
Keywords:Wolbachia, alphaviruses, flaviviruses.
Glasgow Author(s) Enlighten ID:Rainey, Dr Stephanie and Sinkins, Professor Steven and Kohl, Professor Alain and Lefteri, Dr Daniella
Authors: Rainey, S. M., Lefteri, D. A., Darby, C., Kohl, A., Merits, A., and Sinkins, S. P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Viruses
ISSN (Online):1999-4915
Published Online:13 January 2024
Copyright Holders:Copyright © 2024 The Authors
First Published:First published in Viruses 16(1): 115
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.1572

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173477Wolbachia-mediated arbovirus inhibition in mosquitoesSteven SinkinsWellcome Trust (WELLCOTR)202888/Z/16/ZSII - MRC-UofG Centre for Virus Research
174018Wolbachia-based control of virus transmission by the mosquito Aedes albopictusSteven SinkinsWellcome Trust (WELLCOTR)108508/A/15/ZSII - MRC-UofG Centre for Virus Research
168419Wolbachia as a defence against RNA viruses in insects. Wellcome Trust (094664/Z/10/Z)Alain KohlWellcome Trust (WELLCOTR)094664/Z/10/Z- RG61077SII - MRC-UofG Centre for Virus Research
172630007Arthropod-borne infections and emerging virus infections in high risk areas (Programme 4)Alain KohlMedical Research Council (MRC)MC_UU_12014/8III - Centre for Virus Research