Extended Data Figure 10: Treatment with a caspase1 inhibitor does not increase productive HIV-1 infection.

To determine whether inhibition of caspase-1-mediated pyroptosis would result in higher levels of productive HIV-1 infection, tonsillar HLACs were treated with AMD3100 or with the caspase 1 inhibitor Ac-YVAD-CMK before infection with a GFP reporter virus (NLENG1). After 5 days, flow cytometry analysis of the infected cultures revealed no increase in GFP-positive cells in the infected cultures treated with the caspase 1 inhibitor Ac-YVAD-CMK. This result likely reflects the continued function of the host restriction factor SAMHD1 (refs 35, 69). These findings argue against the possibility that pyroptosis functions as a defence against productive infection. Instead, pyroptosis appears to represent an overall harmful response that centrally contributes to HIV pathogenesis. These results also argue that interdiction of the pyroptosis pathway with caspase 1 inhibitors would produce beneficial rather than harmful therapeutic effects.