*2.4. Induction of Apoptosis*

Apoptosis inducers were added 2 h post-infection (hpi) or 2 h before infection (hbi) for ZIKV infected cells. For the replicons, cells were treated 24 h after transfection or passage of stable cells.

For extrinsic apoptosis, cells were treated 2 hpi or 2 hbi with TNFα (10 ng.mL−1) and cycloheximide (10 μg.mL−1) (TNFα/CHX). The addition of cycloheximide prevents the activation of NFkB and the inhibition of apoptosis [24]. Drugs were added as indicated in the figure legends, before quantification of cell death.

For intrinsic apoptosis, etoposide at 10 μM or blasticidin at 5 μg.mL−<sup>1</sup> (InvivoGen, Toulouse, France) were added 16 h to 18 h as indicated in the legends. Alternatively, cells were treated with a dose of 400 mJ of UV (Uvitec, Cambridge, UK) and collected for death measurements 16 h after treatment.

For inhibition of the anti-apoptotic Bcl-2 family proteins, ABT-737 (1 μM) was added at the same time as TNF/CHX and the cells were treated as above. Previous experiments were set-up to show that ABT-737 alone under these conditions did not induce cell death (Figure 8B).
