These findings indicate that after primary infection with varicella-zoster virus (varicella), the virus becomes latent in many ganglia--more often in the trigeminal ganglia than in any thoracic ganglion--and that more than one region of the viral genome is present during latency.

Reactivation of varicella-zoster virus (VZV) leads to localized zoster (shingles), a syndrome characterized by pain and a vesicular rash. Rarely, patients experience radicular pain without zosteriform rash, cases that have been regarded as zoster sine herpete (zoster without rash). Virologic evidence for zoster sine herpete is sparse. However, VZV can produce other neurologic and visceral diseases in the absence of rash or radicular pain. The clinical and virologic features of zoster sine herpete and other disorders produced by VZV without rash are reviewed. Evidence is also presented for the detection of VZV DNA in human blood mononuclear cells of elderly individuals in the absence of skin lesions or other VZV-associated neurologic or systemic disease.

Human dorsal root ganglia from 14 randomly autopsied adults and 1 infant (all seropositive for both herpes simplex virus [HSV] and varicella zoster virus [VZV]) were examined for latent HSV-1 and VZV DNA by polymerase chain reaction. Thoracic ganglionic DNA from all subjects and trigeminal ganglionic DNA from 11 adults were analyzed. HSV-1 DNA was detected in trigeminal ganglia from 8 of 11 (73%) adults and in thoracic ganglia from 2 of 14 (14%) adults. VZV DNA was detected in trigeminal ganglia from 10 of 11 (91%) adults and in thoracic ganglia from 12 of 14 (86%) adults. None of the DNA samples were positive with primers specific for HSV-2. These findings indicate the presence of latent HSV-1 and VZV DNA in trigeminal ganglia and latent VZV DNA in thoracic ganglia of most seropositive adults. Furthermore, although HSV-1 latency most commonly develops in trigeminal ganglia, we also show for the first time the presence of HSV-1 latency in thoracic ganglia. Finally, both viruses can become latent in the same trigeminal ganglion.

Clinical, pathological, immunological, and virological evidence suggests that simian varicella virus (SW) infection of primates is the counterpart ofvaricella-zoster virus infection of humans. To determine whether these two viruses share similrities in their properties during latency, we analyzed ganglia and brain of an African green monkey experimentally infected with SW for the presence of viral nucleic acid using the polymerase chain reaction technique. We detected SW DNA in dorsal root ganglia but not in brain of this monkey, which demonstrated no apparent clinical signs of SW infection. Ohr results suggest that SW becomes latent in monkey ganglia and that latency can develop in the absence of clinical varicella (chickenpox). These studies provide an animal model system to study varicella virus latency.Varicella-zoster virus (VZV) causes chickenpox (varicella) in childhood, becomes latent in dorsal root ganglia, and reactivates decades later to produce shingles (zoster) in adults. The host range of VZV is restricted exclusively to humans,' so that no animal model has been developed to study VZV pathogenesis and latency. However, there have been various reports of spontaneous epizootic outbreaks of varicella in housed monkeys. Like human varicella, simian varicella frequently occurs in epidemics, has an incubation period of 1 or more weeks, and histologic examination of skin lesions reveals necrosis and hemorrhagic foci of epidermal cells containing intranuclear inclusions (1). The causative agent of simian varicella is a member of the herpesvirus family, simian varicella virus (SVV), which is antigenically crossreactive with VZV (2, 3). SVV also reactivates in monkeys to produce disseminated varicella (3). If the'site of SVV latency is ganglionic as has been shown for human VZV (4, 5), then studies of SVV pathogenesis and latency in primates would be relevant to human VZV infection. In the present study, we demonstrate the presence of latent SVV DNA in ganglia and the establishment of latent infection in a monkey which seroconverted after experimental infection with SVV but failed to develop clinical varicella. METHODS SW. The deltaherpesvirus (DHV) strain of SVV was originally isolated from a naturally infected patas monkey (Erythocebus patas) as described (6) and propagated in Vero cells, and a virus stock was prepared as described (7,8).Virus Inoculation. A 6-year-old female African green monkey (Cercopithecus aethiops) was inoculated with SVV as described (8). Briefly, 105 plaque-forming units of SVV in 1.5 ml was administered by intratracheal catheter into the upper bronchi, and 1.5 ml was injected subcutaneously over the abdomen. Two days after inoculation, the monkey was treated intramuscularly with a purine nucleoside, B722U (Burroughs Wellcome), at 150 mg/kg of body weight per day for 10 days. The monkey was examined daily for a varicelliform eruption. Blood was collected every few days for detection of viremia and on days 14 and 21 after inoculation for determination of antibody titer to SV...

We have encountered six zoster patients whose pain preceded rash by 7 to more than 100 days. Pain was severe, burning, and radicular, and located both in dermatomes different from, as well as in, the area of eventual rash. Two patients ultimately developed disseminated zoster with neurologic complications, one of zoster paresis, and the other, a fatal zoster encephalitis; both had been taking long-term, low-dose steroids. A third case of preherpetic neuralgia developed in a patient with prior metastatic carcinoma, and another case in a patient with an earlier episode of brachial neuritis. The final two cases of preherpetic neuralgia developed in individuals with no underlying disease. An extended period of pain before the onset of zoster rash has gone largely unrecognized.