Evidence of Differences in Cellular Regulation of -Mediated Viral Inhibition between Alphaviruses and Flaviviruses.

The intracellular bacterium is increasingly being utilised in control programs to limit the spread of arboviruses by mosquitoes. Achieving a better understanding of how 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 , perturbations in lipid metabolism and cholesterol storage are vital in -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 cells, we found that strains Mel, Au and 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 cells and in vivo in stable, transinfected mosquito lines. The strains Mel, Au and 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 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 in comparison to flaviviruses.