While knockdown of TRAF6 or IKK-β expression did not attenuate HIV infection (Figure 5E and Supplemental Figure 3M), there was a robust reduction in HIV-1 icRNA-induced IP-10 and IFN-β mRNA expression upon knockdown of TRAF6 or IKK-β expression in MDMs (Figure 5F, Supplemental Figure 2T, and Supplemental Figure 3N), indicating an important role of TRAF6 and IKK-β in MDA5/MAVS-dependent activation of IRF5 for induction of IP-10 and type I IFN responses in HIV-1–infected macrophages. Here, IFIH1 is linked to HIV infectious disease.