Evidence of Differences in Cellular Regulation of Wolbachia-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
Author:
Rainey Stephanie M.1ORCID, Lefteri Daniella A.1ORCID, Darby Christie1, Kohl Alain12, Merits Andres3ORCID, Sinkins Steven P.1ORCID
Affiliation:
1. MRC-University of Glasgow-Centre for Virus Research, Garscube Campus, University of Glasogw, Glasgow G61 1QH, UK 2. Departments of Tropical Disease Biology and Vector Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK 3. Institute of Technology, University of Tartu, 50411 Tartu, Estonia
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.
Funder
Wellcome Trust Medical Research Council
Subject
Virology,Infectious Diseases
Reference35 articles.
1. Long term prevention and vector control of arboviral diseases: What does the future hold?;Mota;Int. J. Infect. Dis.,2019 2. Establishment of Wolbachia Strain wAlbB in Malaysian Populations of Aedes aegypti for Dengue Control;Nazni;Curr. Biol.,2019 3. Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue;Utarini;N. Engl. J. Med.,2021 4. Pinto, S.B., Riback, T.I.S., Sylvestre, G., Costa, G., Peixoto, J., Dias, F.B.S., Tanamas, S.K., Simmons, C.P., Dufault, S.M., and Ryan, P.A. (2021). Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói, Brazil: A quasi-experimental study. PLoS Negl. Trop. Dis., 15. 5. Rainey, S.M., Martinez, J., McFarlane, M., Juneja, P., Sarkies, P., Lulla, A., Schnettler, E., Varjak, M., Merits, A., and Miska, E.A. (2016). Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways. PLOS Pathog., 12.
|
|