Multiple mechanisms for HSV-1 induction of interferon alpha production by peripheral blood mononuclear cells.
UV-inactivated, infectious, and other forms of herpes simplex virus 1 (HSV-1) induced interferon (IFN) production by different routes in myeloid origin mononuclear cells (MOMC) (consisting predominantly of monocytes). GM-CSF activated the MOMC (G-MOMC) to produce greater amounts of interferon while differentiation to DC, by the addition of granulocyte macrophage colony stimulating factor (GM-CSF) and calcium ionophore (GA-MOMC), reduced the levels of interferon production upon challenge with some HSV strains. UV-inactivated virus induced more interferon than infectious virus. L-fucose, an antagonist of the mannose receptor, inhibited the induction of IFN-alpha by UV-inactivated virus and gB(-) virus (defective in penetration) in MOMC and GA-MOMC but not G-MOMC. L-fucose had little effect on interferon induction by infectious HSV-1. The insensitivity of the G-MOMC to fucose inhibition distinguishes these interferon producing cells from the pDC2 cells previously described as natural interferon producing cells. The mannose receptor appears to be involved in the response to non-infectious forms of HSV but infectious virus appears to use a different pathway. These studies suggest that non-infectious virions and HSV infected cell debris effectively stimulate monocytes and pre-dendritic cells to produce IFN-alpha to initiate host protection against HSV infection.
Rong
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Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
Alexander
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Koski
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GK
Rosenthal
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KS
D005643:Fucose / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D009154:Mutation; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D013045:Species Specificity; D014779:Virus Replication
D016898:Interferon-alpha; D005643:Fucose