Multiple mechanisms for HSV-1 induction of interferon α production by peripheral blood mononuclear cells

Abstract

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.

Herpes Simplex Virus Type-1-Induced Activation of Myeloid Dendritic Cells: The Roles of Virus Cell Interaction and Paracrine Type I IFN Secretion

“…The DC receptors involved in inducing this IFN secretion are currently unspecified. Important candidates include chemokine receptors (28) and the mannose receptor, which has been implicated in the secretion of type I IFN by DC in response to HSV-1 (29,30). Nevertheless, the data presented in this study strongly suggest that the stimulus for type I IFN secretion in MDDC to this DNA virus is independent of viral replication and therefore of the production of viral RNA, and thus differs from the mechanisms proposed for some RNA viruses (27).…”

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

“…IFN-a/b is immediately induced after viral attachment, recognition by Toll-like receptors, or after infection and replication in cells [11,12]. IFN-a/b induces at least a few hundred genes and orchestrates the defense [13][14][15] via direct inhibition of viral replication [16,17], the activation of NK cells [18], macrophages [19] and DC [20][21][22][23], and the enhancement of T cell stimulation [24,25].…”

Early Alpha/Beta Interferon Production by Myeloid Dendritic Cells in Response to UV-Inactivated Virus Requires Viral Entry and Interferon Regulatory Factor 3 but Not MyD88

“…Myeloid DCs (mDCs) are also capable of IFN-␣/␤ production in response to replicating virus (13,22,45,46,55,57). However, only a few reports (45,46,55) describe an ability of mDCs to produce IFN-␣/␤ in response to virus independent of replication.…”