LOSS OF ABILITY TO PRODUCE IFN-ALPHA IN RESPONSE TO HIV-1 AS MONOCYTES DIFFERENTIATE INTO MACROPHAGES - INDUCTION THROUGH A MECHANISM INDEPENDENT OF DOUBLE-STRANDED-RNA

IFN-alpha is an antiviral cytokine detected in plasma of HIV-1-infecte d patients during acute viremia and during late-stage disease. Monocyt es produced IFN-alpha in response to HIV-1: 1) IFN-alpha was produced predominantly by adherent cells; 2) depleting CD14(+) cells nearly abo lished HIV-1-induced IFN-alpha production; and 3) intracytoplasmic IFN -alpha was detected in CD14(+) cells. During cell culture, monocytes d ifferentiated into macrophages and lost their ability to produce IFN-a lpha when challenged with HIV-1. These cells remained capable of produ cing IFN-alpha in response to other stimuli such as poly(I:C), a synth etic dsRNA. Thus, we examined two negative-stranded RNA viruses that h ave dsRNA intermediates, Newcastle disease virus and Sendai virus, and a DNA virus, herpes simplex virus type 1 (HSV-1). Macrophages lost th eir ability to produce IFN-1 in response to HSV-1, but not to Sendai v irus or to Newcastle disease virus, Thus, HIV-1 and other viruses were capable of inducing IFN-alpha through a mechanism that was independen t of dsRNA, In conclusion, these data suggest that there are dsRNA-dep endent and -independent mechanisms for the induction of IFN-alpha prod uction, and that as monocytes differentiate into macrophages, they sel ectively lose their ability to produce IFN-alpha through the dsRNA-ind ependent mechanism.