Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses

The intracellular bacterium <i>Wolbachia</i> is increasingly being utilised in control programs to limit the spread of arboviruses by <i>Aedes</i> mosquitoes. Achieving a better understanding of how <i>Wolbachia</i> strains can reduce viral replication/spread coul...

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Main Authors: Stephanie M. Rainey, Daniella A. Lefteri, Christie Darby, Alain Kohl, Andres Merits, Steven P. Sinkins
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/16/1/115
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author Stephanie M. Rainey
Daniella A. Lefteri
Christie Darby
Alain Kohl
Andres Merits
Steven P. Sinkins
author_facet Stephanie M. Rainey
Daniella A. Lefteri
Christie Darby
Alain Kohl
Andres Merits
Steven P. Sinkins
author_sort Stephanie M. Rainey
collection DOAJ
description The intracellular bacterium <i>Wolbachia</i> is increasingly being utilised in control programs to limit the spread of arboviruses by <i>Aedes</i> mosquitoes. Achieving a better understanding of how <i>Wolbachia</i> 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 <i>Wolbachia</i>, perturbations in lipid metabolism and cholesterol storage are vital in <i>Wolbachia</i>-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 <i>Aedes albopictus</i> cells, we found that <i>Wolbachia</i> strains <i>w</i>Mel, <i>w</i>Au and <i>w</i>AlbB 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 <i>Aedes albopictus</i> cells and in vivo in stable, transinfected <i>Aedes aegypti</i> mosquito lines. The strains <i>w</i>Mel, <i>w</i>Au and <i>w</i>AlbB 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 <i>w</i>Mel 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 <i>Wolbachia</i> in comparison to flaviviruses.
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spelling doaj.art-f9dc37b963a94dd1b7e2ea3dcc203aaa2024-01-26T18:48:18ZengMDPI AGViruses1999-49152024-01-0116111510.3390/v16010115Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and FlavivirusesStephanie M. Rainey0Daniella A. Lefteri1Christie Darby2Alain Kohl3Andres Merits4Steven P. Sinkins5MRC-University of Glasgow-Centre for Virus Research, Garscube Campus, University of Glasogw, Glasgow G61 1QH, UKMRC-University of Glasgow-Centre for Virus Research, Garscube Campus, University of Glasogw, Glasgow G61 1QH, UKMRC-University of Glasgow-Centre for Virus Research, Garscube Campus, University of Glasogw, Glasgow G61 1QH, UKMRC-University of Glasgow-Centre for Virus Research, Garscube Campus, University of Glasogw, Glasgow G61 1QH, UKInstitute of Technology, University of Tartu, 50411 Tartu, EstoniaMRC-University of Glasgow-Centre for Virus Research, Garscube Campus, University of Glasogw, Glasgow G61 1QH, UKThe intracellular bacterium <i>Wolbachia</i> is increasingly being utilised in control programs to limit the spread of arboviruses by <i>Aedes</i> mosquitoes. Achieving a better understanding of how <i>Wolbachia</i> 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 <i>Wolbachia</i>, perturbations in lipid metabolism and cholesterol storage are vital in <i>Wolbachia</i>-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 <i>Aedes albopictus</i> cells, we found that <i>Wolbachia</i> strains <i>w</i>Mel, <i>w</i>Au and <i>w</i>AlbB 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 <i>Aedes albopictus</i> cells and in vivo in stable, transinfected <i>Aedes aegypti</i> mosquito lines. The strains <i>w</i>Mel, <i>w</i>Au and <i>w</i>AlbB 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 <i>w</i>Mel 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 <i>Wolbachia</i> in comparison to flaviviruses.https://www.mdpi.com/1999-4915/16/1/115<i>Wolbachia</i>alphavirusesflaviviruses
spellingShingle Stephanie M. Rainey
Daniella A. Lefteri
Christie Darby
Alain Kohl
Andres Merits
Steven P. Sinkins
Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
Viruses
<i>Wolbachia</i>
alphaviruses
flaviviruses
title Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
title_full Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
title_fullStr Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
title_full_unstemmed Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
title_short Evidence of Differences in Cellular Regulation of <i>Wolbachia</i>-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
title_sort evidence of differences in cellular regulation of i wolbachia i mediated viral inhibition between alphaviruses and flaviviruses
topic <i>Wolbachia</i>
alphaviruses
flaviviruses
url https://www.mdpi.com/1999-4915/16/1/115
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