Arch Virol (2002) 147: 763–773
The ability of an HSV strain to initiate zosteriform spread
correlates with its neuroinvasive disease potential
, J. J. Docherty
, and K. S. Rosenthal
Northeastern Ohio Universities College ofMedicine, Rootstown, Ohio, U.S.A.
Cel-Sci Corporation, Vienna, Virginia, U.S.A.
Accepted November 12, 2001
Summary. The requirements for disease development in the mouse epidermal
scariﬁcation-zosteriform model of HSV infection are likely to parallel those re-
quired for primary HSV disease of humans. HSV-1 strains, which are neuroinva-
sive in the mouse footpad model of HSV encephalitis, caused local site lesions
within 3 days and secondary zosteriform lesions along the dermatome within ap-
proximately 5 days. HSV-1 strains, which arenot neuroinvasive, failed to progress
to zosteriform lesion development and local site lesions were mild or absent. Rela-
tive differences in the rate and extent of zosteriform lesion development paralleled
the behavior ofthe viruses in the mouse footpad model ofneuroinvasion. In con-
clusion, the viral properties which are important for neuroinvasiveness appear to
also determine the ability ofan HSV strain to cause zosteriform disease.
The development ofherpes simplex virus (HSV) disease is dependent upon both
viral and host properties and different strains of virus have different levels of
disease potential [3, 6]. The pathogenicity ofHSV has been investigated in dif-
ferent animal models, each of which have their similarities and differences from
the primary and latent-recurrent human infections. Mouse models are popular
for the study ofthe pathology ofHSV infections because ofthe size and cost of
the animals and also the availability ofdeﬁned inbred strains. Well characterized
immunology reagents are also available for mice .
The ﬂank scariﬁcation model has been used to evaluate the efﬁcacy of anti-
viral drugs and vaccines [2, 10, 15], and recently, the ability ofHSV-1 strains with
mutations in glycoprotein E to spread within the skin . A very shallow cut or
scrape on the ﬂank ofa mouse is made near the spine to expose the epidermal
cells to the virus. Infection ofthe upper layers ofthe skin optimizes subsequent