Capsaicin-sensitive peptidergic neurons are involved in the zosteriform spread of herpes simplex virus infection.

The intraneuronal transport of herpes simplex virus (HSV) is an essential component in disease pathogenesis. Capsaicin, a neuropharmacologic agent lacking direct antiviral activity, has been shown to protect animals against HSV-induced disease. It has been hypothesized that capsaicin acts by interfering with the intraneuronal transport of virus.

Assessment of a selective inhibitor of herpes simplex virus thymidine kinase (L-653,180) as therapy for experimental recurrent genital herpes.

Herpes simplex virus (HSV)-coded thymidine kinase (TK) is important in efficient reactivation of latent infection. These studies were designed to investigate whether treatment of latently infected animals with a TK inhibitor altered the natural history of recurrent HSV disease. 9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) is a potent and selective nonsubstrate inhibitor of HSV TK which can suppress or delay reactivation of HSV-1 from latently infected cells in vitro without affecting viral replication.

Outcome of herpes simplex virus type 2 infection in guinea pigs.

Factors that influence the outcome of genital herpes simplex virus (HSV) infection were explored in a guinea pig model. The viral inoculum required to establish infection in 50% of animals (ID50) was similar for inbred (strain 2) and outbred (Hartley) guinea pigs. However, the viral inoculum required to produce clinical disease in 50% of the animals (CD50) was 10 times greater for strain 2 compared to Hartley animals.

Evaluation of herpes simplex virus vaccines in animals: the guinea pig vaginal model.

The guinea pig model of genital herpes has proved useful for the evaluation of experimental herpes simplex virus vaccines. The model shares many of the features of genital herpes in humans, including a natural route of inoculation that results in self-limiting primary vulvovaginitis. Latent infection is established in sensory ganglia, and animals experience both spontaneous and ultraviolet radiation-induced recurrence of infection.

Cell-mediated immunologic responses and recurrent genital herpes in the guinea pig. Effects of glycoprotein immunotherapy.

The specific immune alterations associated with HSV recurrences are ill defined although it appears that alterations in cell-mediated immune mechanisms are more likely associated with recurrent disease than humoral immunity. Immunization with HSV glycoproteins B and D (gBgD) after primary HSV infection has reportedly reduced the frequency of recurrences but the mechanisms remain unidentified. We therefore evaluated the effects of immunization with cloned gBgD on selected cell-mediated immune responses and their relationship to recurrent disease by using the guinea pig model of genital HSV-2 infection.

Drug testing for activity against varicella-zoster virus in hairless guinea pigs.

Inoculation of congenitally hairless guinea pigs with varicella-zoster virus (VZV) (Oka strain) results in a self-limited exanthematous infection analogous to varicella in children. Administration of acyclovir or 6-methoxypurine arabinoside modified the course of infection. This model should facilitate pre-clinical testing of putative anti-VZV agents.

Effects of cytokines and R-837, a cytokine inducer, on UV-irradiation augmented recurrent genital herpes in guinea pigs.

We have recently reported that latently HSV-2-infected guinea pigs exhibit a three- to four-fold increase in recurrent lesions after exposure to ultraviolet radiation (UV), allowing rapid evaluation of antiviral drugs in treating recurrent HSV disease. In this report we examine the effect of alpha interferon (IFN-alpha), interleukin-2 (IL-2), and a cytokine inducer (R-837) on UV-induced recurrent genital herpes. We have previously shown that topical R-837 is a biologic response modifier with no in vitro anti-HSV activity, but with potent anti-HSV activity in vivo due to cytokine induction and enhancement of cell-mediated immune responses.

Varicella in hairless guinea pigs.

A high proportion of depilated newborn or euthymic congenitally hairless adult guinea pigs develop an erythematous papular exanthem during infection with varicella-zoster virus (VZV) previously cultivated in guinea pig cell culture. Virus has been demonstrated in tissues during varicella using polymerase chain reaction amplification and nucleic acid hybridization methods. The frequency of exanthem expression can be reduced by the prophylactic administration of VZV convalescent-phase guinea pig serum.

Capsaicin interferes with the centrifugal spread of virus in primary and recurrent genital herpes simplex virus infections.

The neural spread of herpes simplex virus (HSV) via sensory nerves is an essential component of disease pathogenesis. Capsaicin, a specific toxin for sensory C-type fibers, interferes with neuronal function including axonal transport. Capsaicin treatment of guinea pigs before intravaginal HSV inoculation did not prevent ganglionic infection but ameliorated cutaneous herpetic disease, suggesting that anterograde but not retrograde virus spread involved a capsaicin-sensitive process.

Recurrent genital herpes in the guinea pig augmented by ultraviolet irradiation: effects of treatment with acyclovir.

The guinea pig model of genital herpes simplex virus infection has proven useful in the evaluation of antiviral drugs. We have recently demonstrated that recurrent herpetic infections can be induced in latently infected guinea pigs by ultraviolet irradiation. In this report we have examined the effect of acyclovir on ultraviolet radiation-induced recurrent genital herpes.

Detection of asymptomatic initial herpes simplex virus (HSV) infections in animals immunized with subunit HSV glycoprotein vaccines.

The evaluation of herpes simplex virus (HSV) vaccine efficacy will require methods to detect asymptomatic acquisition of HSV infection and to assess the risk of recurrences in these patients. HSV-infected vaccinees should develop antibodies to HSV polypeptides not included in subunit vaccines. Sera from 57 HSV glycoprotein-vaccinated guinea pigs that had asymptomatic initial infections after genital HSV type 2 challenge were collected after vaccination but before HSV challenge and again 30 days after HSV challenge to determine the antibody response to HSV polypeptides.

Preinfection prophylaxis with herpes simplex virus glycoprotein immunogens: factors influencing efficacy.

Using a guinea-pig model of genital herpes simplex virus (HSV) infection we explored the protection afforded by preinfection immunization with HSV glycoproteins. Glycoprotein immunogens prepared by recombinant DNA technology were found to be as effective as immunogens purified from HSV-infected cell cultures. Immunized animals developed less severe primary disease and also experienced less frequent recurrent infections.

Animal model of ultraviolet-radiation-induced recurrent herpes simplex virus infection.

The development of a model of induced recurrent herpes simplex virus disease would facilitate studies of the mechanism(s) responsible for reactivation of latent virus. The guinea pig model of genital herpes is characterized by a self-limited primary infection, the establishment of a latent infection in sensory ganglia, and the subsequent development of spontaneous recurrent genital infections. This study reports that exposure of latently infected female guinea pigs to ultraviolet radiation results in the induction of recurrent genital herpes simplex virus infections in approximately 60% of animals.

Herpes simplex virus glycoprotein immunotherapy of recurrent genital herpes: factors influencing efficacy.

Recombinant herpes simplex virus type 1 (HSV-1) glycoproteins B (gB) and D (gD) were used as immunotherapeutic agents for the treatment of recurrent genital herpes in guinea pigs. Administration of a gBgD vaccine eight to 21 days after intravaginal HSV-2 inoculation significantly increased the titer of anti-HSV antibodies (P less than 0.005) while significantly reducing the frequency of subsequent herpetic recurrences (P less than 0.

Herpes simplex virus glycoprotein treatment of recurrent genital herpes reduces cervicovaginal virus shedding in guinea pigs.

Treatment of previously infected guinea pigs with herpes simplex virus (HSV) glycoproteins reduces the frequency and severity of subsequent genital recurrences. An effective vaccine should also reduce episodes of viral shedding. In this study, HSV glycoproteins B and D treatment of animals experiencing recurrent genital herpes reduced the frequency of both clinical recurrences and cervicovaginal viral shedding.

Evaluation of varicella-zoster antiviral drugs by a nucleic acid hybridization assay.

A simple nucleic acid hybridization assay was developed for the evaluation of antiviral compounds with activity against varicella-zoster virus. Antiviral-induced reduction in varicella-zoster virus DNA, as measured by hybridization with 32P-labeled probes, correlated with drug-induced inhibition of viral cytopathic effect in cell culture. Three compounds were shown to be more potent than acyclovir at inhibiting varicella-zoster virus in vitro.

Antibody to herpes simplex virus (HSV) ICP-35 proteins after HSV challenge of animals immunized with HSV subunit vaccines.

The serological response to the ICP-35 group of herpes simplex virus type 2 (HSV-2) proteins was examined 30 d after vaginal challenge with HSV-2 of guinea pigs previously immunized with HSV glycoproteins. Detection of antibodies to ICP-35 proteins correlated best with the magnitude of vaginal viral replication. Animals that developed antibody to ICP-35 proteins had more-frequent recurrences (P less than .

Herpes simplex virus glycoprotein treatment of recurrent genital herpes.

We investigated the possibility that herpes simplex virus (HSV) glycoproteins might provide potential immunotherapy for recurrent HSV disease by using the guinea pig model of genital HSV infection. In two experiments, after recovery from initial genital herpes, 58 animals were randomized either to receive a glycoprotein vaccine or to serve as controls. Both a mixture of HSV-2 glycoproteins derived from infected tissue cultures and a mixture of HSV-1 glycoproteins B and D, prepared by genetic engineering in mammalian cells, reduced the frequency (P less than .

Varicella in a gorilla.

Naturally occurring varicella was observed in a young gorilla in captivity. The isolate was demonstrated to be varicella-zoster virus by restriction enzyme analysis.

Antibody response to herpes simplex virus glycoprotein D: effects of acyclovir and relation to recurrence.

We developed an enzyme-linked immunosorbent assay (ELISA) for measuring the antibody response to herpes simplex virus (HSV) glycoprotein D (gD). The ELISA was specific and more sensitive than immunoblotting techniques. Antibody to HSV gD was detected in 10 of 12 sera (geometric mean titer, 36.

Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes.

The natural history of initial and subsequent recurrent herpes simplex virus (HSV) genital infection was studied in guinea pigs immunized with HSV glycoprotein vaccines before vaginal challenge with HSV-2. The vaccines used included HSV-1 glycoprotein B and HSV-1 glycoprotein D, both prepared by recombinant DNA techniques, and mixtures of HSV-1 or HSV-2 glycoproteins, prepared from infected cell monolayers by lectin chromatography. Immunizing guinea pigs with subunit HSV glycoprotein vaccines favorably altered the clinical and virological course of initial infection and substantially reduced the incidence, frequency, and duration of recurrent herpetic infections.

Zosteriform spread of herpes simplex virus type 2 genital infection in the guinea-pig.

A model of herpes simplex virus type 2 (HSV-2) infection was developed in the guinea-pig that permits investigation of the role of neural spread of virus in the pathogenesis of genital skin disease. After HSV-2 inoculation of an abraded area lateral to the external genital skin, virus was first detected in the ipsilateral (to the inoculation site) peripheral nerves or genital skin on day 2 or 3 post-inoculation followed by detection in the ipsilateral dorsal root ganglia and spinal cord on day 3 or 4. Virus also spread to the contralateral dorsal root ganglia, contralateral peripheral nerves and contralateral genital skin on day 4 or 5 although lesions were only rarely detected on the contralateral side.

Antibody response, recurrence patterns and subsequent herpes simplex virus type 2 (HSV-2) re-infection following initial HSV-2 infection of guinea-pigs: effects of acyclovir.

The production of antibody to specific herpes simplex virus type 2 (HSV-2) polypeptides, the recurrence patterns and the susceptibility to re-infection were studied in the guinea-pig model of genital HSV-2 infection. Further, we defined the effects of acyclovir (ACV) therapy on these parameters of infection. Treatment with ACV reduced the clinical severity of the initial disease but did not affect vaginal viral shedding.