Pathogenesis of Herpes Simplex Virus in Congenitally Athymic Mice: the Relative Roles of Cell-mediated and Humoral Immunity

Abstract

SUMMARYAthymic nude (nu/nu) mice were inoculated in the ear pinna with 104 p.f.u, herpes simplex virus type 1 (strain SC 16). Initially, the virus was observed to replicate in the pinna, spreading via a neurological route to the dorsal root ganglia, spinal cord, brain and adrenal glands. Following the transfer of lymphoid cells from day 7 herpesvirus-infected hairy immunocompetent donors into infected nude mice, virus was not isolated from the pinna and nervous system of the majority of the mice. The passive transfer of neutralizing polyclonal anti-herpesvirus Serum or neutralizing monoclonal anti-gp D serum did not reduce infectivity in the pinna, but markedly reduced the amount of virus in the ganglia and spinal cord. These data suggest that neutralizing antibodies play an important role in restricting the movement of virus to the nervous system, whereas cell-mediated immune (CMI) mechanisms are essential for eliminating virus from the pinna.

Passive immunization protects the mouse eye from damage after herpes simplex virus infection by limiting spread of virus in the nervous system

“…However, later spread to other parts of the nervous system is likely to involve extracellular virus (Hill, 1987) which could be neutralized by antibodies. Passively transferred anti-HSV-1 antibodies, given 3 days after inoculation of the pinna were found to reduce the amount of virus reaching the ganglion and spinal cord but did not alter the amount of virus at the inoculation site (Kapoor et al, 1982).…”

“…These clinical observations were supported by the similarity in the two groups of timing and incidence of virus isolation from eye washings and virus antigens in corneal epithelial sheets. Others have reported that passive immunization does not affect titres of virus at the inoculation site during primary infection of the eye (Lausch et al, 1989) or skin (Kapoor et aL, 1982). In contrast, if mice are actively immunized against HSV-1 some time before inoculation of the cornea virus is rapidly cleared from the tears (Tullo et al, 1983).…”

Antiviral Activities of Cloned Human Leukocyte Interferons against Herpes Simplex Virus Type 2 Infections of Mice

“…Such differences in tissue sensitivities to interferon are apparent in the case of other virus infections in mice (Dandoy et al, 1982). Experiments with nude and immunocompetent mice have revealed that the route of inoculation with virus also has an effect on the outcome and host susceptibility to infection (Kapoor et al, 1982). The inference is that different mechanisms of protection, either cell-mediated or humoral, are preferentially induced according to the site of virus inoculation and that the potential of…”

Herpes simplex virus 1 (HSV-1) for cancer treatment

“…Both nonspecific (mediated by macrophages and natural killer cells) and specific immune responses (mediated by B and T cells) have been implicated as important host defenses against HSV-1 infections. [48][49][50][51][52][53] The relative value of each of these defense mechanisms varies significantly according to the genetic background of the host 54,55 and the route of viral inoculation.…”