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- Title
Production of Interferon α by Human Immunodeficiency Virus Type 1 in Human Plasmacytoid Dendritic Cells Is Dependent on Induction of Autophagy.
- Authors
Dejiang Zhou; Kyung Hee Kang; Spector, Stephen A.
- Abstract
Background. The mechanisms responsible for interferon α (IFN-α) production by plasmacytoid dendritic cells (pDCs) during human immunodeficiency virus type 1 (HIV-1) infection are unknown. This research examined the roles of Toll-like receptor 7 (TLR7) and autophagy in IFN-α production by pDCs during HIV-1 infection. Methods. pDCs from human peripheral blood mononuclear cells were incubated with infectious or aldrithiol 2 (AT-2)-inactivated HIV-1 or with uridine-rich single-stranded RNA40 (ssRNA40) from the HIV-1 long terminal repeat. IFN-α was quantified by enzyme-linked immunosorbant assay. Autophagic proteins were detected by Western blot, and autophagosomes were identified using immunofluorescent and confocal microscopy. To inhibit autophagy, pDCs were treated with the phosphoinositide-3 kinase inhibitor 3-methyladenine (3-MA) or were transfected with autophagy-related protein 7 or TLR7 small interfering RNA (siRNA). Results. Increased levels of IFN-α were present in culture supernatants following 16-hour incubation of pDCs with infectious or AT-2-inactivated HIV-1. Treatment of pDCs with ssRNA40 but not ssRNA41 resulted in high levels of IFN-α. pDCs exposed to HIV-1 gp120, rapamycin, or 3-MA alone failed to induce IFN-α. Pretreatment of pDCs with 3-MA significantly reduced the induction of IFN-α by ssRNA40. Similarly, knock down of autophagyrelated protein 7 and TLR7 by use of siRNA significantly reduced the induction of IFN-α by ssRNA40 or HIV-1. Conclusions. These findings demonstrate that IFN-α production by pDCs exposed to infectious or noninfectious HIV-1 and ssRNA40 occurs through induction of autophagy following TLR7 signaling.
- Subjects
INTERFERONS; HIV; PLASMA cells; AUTOPHAGY; SMALL interfering RNA; RAPAMYCIN
- Publication
Journal of Infectious Diseases, 2012, Vol 205, Issue 8, p1258
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jis187