Arch Virol (2000) 145: 1989–2002
Impaired induction of protective immunity by highly virulent
herpes simplex virus type 2 in a murine model of genital herpes
K. Inagaki-Ohara, T. Daikoku, F. Goshima, and Y. Nishiyama
Laboratory of Virology, Research Institute for Disease Mechanism and Control,
Nagoya University School of Medicine, Nagoya, Japan
Accepted May 22, 2000
Summary. Weinvestigatedtheimmuneeventsinthevaginaof mice intravaginally
infected with highly virulent herpes simplex virus type 2 (HSV-2) strain 186, and
compared them with those induced by HSV type 1 strain KOS, a widely known
laboratory strain. Although there was no signiﬁcant difference between 186 and
KOS in the viral replication in the initial stage of infection, inadequate and delayed
clearance of virus from the vaginal mucosa was observed in 186-challenged mice.
The induction of antigen-presenting cells (APC) such as dendritic cells (DC)
and macrophages (M) in the vagina was slow in 186-challenged mice, and the
number of T cells in the vagina in 186-challenged mice was much lower than
that in KOS-challenged mice. Furthermore, the level of IL-12 as well as that of
IFN-␥ was signiﬁcantly lower in 186-challenged mice than in KOS-challenged
mice, while the level of IL-4 in 186-challenged mice was higher than that in KOS-
challenged mice. On the basis of these observations, we suggest that the weak
activation of epithelial cells and the delayed induction of APC by 186-infection
may be involved in the inadequate activation of T cells and the ineffective virus
clearance from the vaginal mucosa.
Herpes simplex virus (HSV) is a sexually transmitted pathogen infecting both the
oral and genital mucosa , and is the most common infective cause of genital
ulceration in the developed countries . The virus spreads from the genital tract
to the nervous system, and latently infects dorsal root ganglia. Activation of the
latent virus causes recurrent lesions in the genital tract and adjacent tissues [7, 8].
HSV type 2 (HSV-2) usually causes severer diseases than HSV type 1 (HSV-1)
in immunocompromised individuals  and in neonates who are infected dur-
ing delivery through the infected birth canal . In addition, genital ulceration
caused by HSVs may facilitate the transmission of the human immunodeﬁciency
virus [6, 14, 21].