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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Abstract
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. |
| Status: | Published |
| Refereed: | Yes |
| 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 |
| Publisher: | MDPI |
| ISSN: | 1999-4915 |
| 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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