Loss 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-infected patients during acute viremia and during late-stage disease. Monocytes produced IFN-alpha in response to HIV-1:1) IFN-alpha was produced predominantly by adherent cells; 2) depleting CD14+ cells nearly abolished HIV-1-induced IFN-alpha production; and 3) intracytoplasmic IFN-alpha was detected in CD14+ cells. During cell culture, monocytes differentiated into macrophages and lost their ability to produce IFN-alpha when challenged with HIV-1. These cells remained capable of producing IFN-alpha in response to other stimuli such as poly(I:C), a synthetic dsRNA. Thus, we examined two negative-stranded RNA viruses that have dsRNA intermediates, Newcastle disease virus and Sendai virus, and a DNA virus, herpes simplex virus type I (HSV-1). Macrophages lost their ability to produce IFN-alpha in response to HSV-1, but not to Sendai virus or to Newcastle disease virus. Thus, HIV-1 and other viruses were capable of inducing IFN-alpha through a mechanism that was independent of dsRNA. In conclusion, these data suggest that there are dsRNA-dependent and -independent mechanisms for the induction of IFN-alpha production, and that as monocytes differentiate into macrophages, they selectively lose their ability to produce IFN-alpha through the dsRNA-independent mechanism.
Francis
M L
ML
Section on Rheumatology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Fan
X S
XS
Meltzer
M S
MS
D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D015497:HIV-1 / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000096:biosynthesis*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D009522:Newcastle disease virus / Q000276:immunology; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology
D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011070:Poly I-C