Arch Virol (2000) 145: 385–396
Herpes simplex virus type-1 and -2 pathogenesis is restricted
by the epidermal basement membrane
B. S. Weeks
, R. S. Ramchandran
, J. J. Hopkins
, and H. M. Friedman
Department of Biology, Adelphi University, Garden City, New York, U.S.A.
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania, U.S.A.
Accepted August 31, 1999
Summary. MurineﬂankscariﬁcationwithHSV-1and -2 results in primary lesions
at the site of inoculation within three days and lesions at secondary sites within
four days. The severity of the infection can be given a numerical value or “score”
which is derived from the number and size of these lesions. Using this model, we
investigated the role of the epidermal basement membrane in HSV pathogenesis.
We exposed murine epidermis to 5×10
plaque forming units of HSV-1 and -2,
which by day 8 produced inoculation site (primary site) disease scores of 27 and
12.4 respectively, and secondary site disease scores of 29 and 30 respectively. In
contrast, intradermal injection of HSV below the epidermal basement membrane
did not cause disease. To determine if the basement membrane restricts HSV
spread in vitro, Vero cells were cultured in the lower well of a dual well system.
The upper well was separated from the lower well by a ﬁlter coated with the
artiﬁcial basement membrane, matrigel. Addition of virus to the upper well failed
to result in either viral accumulation in the lower well or infection of the cells in
the lower well. These data suggest that the basement membrane is a barrier to the
passage and spread of HSV.
Herpes simplex viruses −1 and −2 (HSV) are two of eight herpes viruses which
infect humans [11, 30]. Both of these viruses infect epithelial surfaces and then
move into nervous tissue [7, 30]. Having entered the epithelium, they undergo
replication and infect and destroy neighboring cells. This produces a primary
lesion at the initial site of infection . During the initial infection, viruses
infect sensory nerve endings in the skin or mucosa and travel to the associated
nerve dorsal root ganglion via retrograde axonal transport . It is in the ganglia