Animal model of ultraviolet‐radiation‐induced recurrent herpes simplex virus infection

Abstract

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. Furthermore, there was a dose-response relationship between ultraviolet irradiation and ability to induce recurrent disease. This model should prove useful in further investigations of the pathophysiology of herpes simplex infections.

Combinations of Antiviral and Anti-Inflammatory Preparations for the Topical Treatment of Herpes Simplex Virus Assessed using a Murine Zosteriform Infection Model

“…For example, in the guinea-pig back skin model, topical treatment with foscarnet was effective, although subsequent clinical trials on recurrent infection in man yielded disappointing results (Alenius et al, 1982). Similarly, the guinea-pig model for HSV-2 exhibits recurrent lesions that occur spontaneously or were induced by means of UV-irradiation (Stanberry, 1989). However, the number of animal developing lesions following stimulation is low and the duration of the lesions produced is shorter than observed in human recurrences (Stanberry, 1994).…”

Optimized Viral Dose and Transient Immunosuppression Enable Herpes Simplex Virus ICP0-Null Mutants To Establish Wild-Type Levels of Latency In Vivo

“…Regarding the first point, although quiescent infections can be established in several different cell types (2,9,39,47,59), the relevance of existing "in vitro latency models" to HSV latency in vivo is unclear. Regarding the second point, although the establishment of latency in animal models closely parallels the natural history of HSV infection in humans (22,41,48), the effect of eliminating a viral gene product on reactivation is difficult to study because many HSV mutants replicate poorly in animals.Comparison of the reactivation efficiencies of null mutant viruses to that of wild-type virus is a potentially powerful approach to identifying viral genes involved in HSV reactivation. The effect of a mutation in a given gene on reactivation efficiency can be measured accurately, however, only when equal numbers of mutant and wild-type viral genomes are present in latently infected ganglia at the time of reactivation.…”

“…Regarding the first point, although quiescent infections can be established in several different cell types (2,9,39,47,59), the relevance of existing "in vitro latency models" to HSV latency in vivo is unclear. Regarding the second point, although the establishment of latency in animal models closely parallels the natural history of HSV infection in humans (22,41,48), the effect of eliminating a viral gene product on reactivation is difficult to study because many HSV mutants replicate poorly in animals.…”

Molecular Aspects of Herpes Simplex Virus I Latency, Reactivation, and Recurrence

“…Fundamentally, it involves a switch from viral quiescence to a replicative state within the neuron that may occur spontaneously or as a result of physical and emotional stress (reviewed in Roizman and Sears, 1996). In experimental animals and humans, reactivation is associated with axonal injury (Carton and Kilbourne, 1952;Walz et al, 1974;McLennan and Darby, 1980), traumatization of peripheral tissues (Hill et al, 1978;Valyi-Nagy et al, 1991), tooth extraction (Openshaw and Bennett, 1982), orofacial fracture (Kameyama et al, 1989), iontophoresis with epinephrine, timolol, and dexamethasone (Kwon et al, 1981;Gordon et al, 1986;Harwick et al, 1987;Hill et al, 1987), administration of prostaglandins, ultraviolet light radiation IUVRI (Wheeler, 1975;Blyth et al, 1976;Perna et al, 1987;Stanberry, 1989;Laycock et al, 1991), cadmium (Fawl and Roizman, 1993), transient hyperthermia (Sawtell and Thompson, 1992a;Moriya et a)., 1994), and immunosuppression with cyclophosphamide and prednisolone (Hurd and Robinson, 1977). Ex vivo, reactivation of HSV-1 occurs following explantation of latently infected human neurons (Baringer and Swoveland, 1973) and following superinfection of latently infected, explanted cultures with HSV-2 temperature-sensitive mutants (Lewis et al, 1984).…”

“…For example, UVR is a potent and predictable stimulus of epithelial erythema (i.e., inflammation) and recurrent disease in humans and guinea pigs (Perna et al, 1987;Stanberry, 1989) and herpetic keratitis in the mouse (Blyth et al, 1976;Harbour et al, 1983;Shimeld et al, 1990). However, UVR does not induce reactivation of HSV-1 from latently infected murine trigeminal ganglia (Birmanns et al, 1993) or latently infected neurons in vitro (Wilcox et at., 1990).…”