Since IRF5 is an ISG (46), and HIV-1 infection of macrophages induces type I IFN responses, we next sought to determine if IRF5 activation in HIV-infected MDMs occurs directly downstream of MDA5/MAVS sensing of HIV icRNA in a cell-intrinsic manner in infected cells or requires activation in bystander uninfected cells. The gene discussed is IFIH1; the disease is HIV-1 infection.