Orellana and colleagues observed that the function of the pannexin-1 ATP-release hemichannel was transiently increased during early infection with both R5 and X4 tropic HIV-1 and that HIV-1 envelope binding to CD4 and coreceptors (both CXCR4 and CCR5) activates pannexin-1 channel opening as a feed-forward signal which can enable HIV-1 internalization in CD4+ T cells (103). Here, CCR5 is linked to infection.