Arch Virol (2003) 148: 329–344
Multiple mechanisms for HSV-1 induction of interferon α
production by peripheral blood mononuclear cells
, T. S. Alexander
, G. K. Koski
, and K. S. Rosenthal
Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, U.S.A.
Summa Health System, Akron, Ohio, U.S.A.
University of Pennsylvania Medical Center, Philadelphia,
Received April 1, 2002; accepted August 17, 2002
Published online November 8, 2002
Summary. 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 in-
terferon while differentiation to DC, by the addition of granulocyte macrophage
colony stimulating factor (GM-CSF) and calcium ionophore (GA-MOMC), re-
duced 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-α 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-α to initiate host protection against HSV infection.
Interferon alpha (IFN α) production is one of the earliest responses to virus
infection, acting locally and systemically  to inhibit virus replication and induce
protective immune responses. IFN α can inhibit infection and the spread of HSV
from neurons to epidermal cells  in vitro, and application of plasmid DNA