Early studies in primary CD4 + T-cells, macrophages, and transformed T-cell lines suggested that uncoupling CCR5 from Gαi signaling does not alter HIV entry [33, 353–357], but more recent data contradict these findings, showing a requirement for G-protein signaling for viral entry and fusion [281, 358–360], or even post-entry stages of infection [361–366]. This evidence concerns the gene CD4 and infection.