Varicella-Zoster Virus DNA in Cells Isolated from Human Trigeminal Ganglia

Abstract

To determine the type of cell(s) that contain latent varicella-zoster virus (VZV) DNA, we prepared pure populations of neurons and satellite cells from trigeminal ganglia of 18 humans who had previously had a VZV infection. VZV DNA was present in 34 of 2,226 neurons (1.5%) and in none of 20,700 satellite cells. There was an average of 4.7 (range of 2 to 9) copies of VZV DNA per latently infected neuron. Latent VZV DNA was primarily present in large neurons, whereas the size distribution of herpes simplex virus DNA was markedly different.Varicella-zoster virus (VZV) is present in a latent form in sensory ganglia of humans who have had a primary infection (varicella) with VZV (11). This is demonstrated by the reactivation of VZV in these individuals as herpes zoster and by the presence of VZV DNA and proteins in ganglia recovered at autopsy (2,3,5,9,10,12,13,15,16,19,20,(22)(23)(24)26). Different laboratories have ascribed the site of latency to either neurons (12-14, 18, 22) or perineuronal satellite cells (5, 26); some laboratories suggest that neurons are the primary site of latency together with a smaller proportion of satellite cells containing the VZV genome (16,20). The primary aim of the experiments described here was to determine the type of cell in trigeminal ganglia that harbors latent VZV and also to obtain data on the proportion of these cells that contain latent VZV. One reason why the site of VZV latency has remained an open question is that neurons and satellite-supporting cells are tightly associated in ganglia and the in situ methods used to locate VZV DNA did not clearly resolve the source of the hybridization signal. This resolution was easier for latent HSV because a strong hybridization signal to HSV facilitated its localization to the nucleus of the neuron. In contrast, the hybridization signal from VZV DNA is considerably weaker and dispersed over both nucleus and cytoplasm. While the hybridization methodology has improved, these considerations remain (21, 30). To reduce the ambiguities inherent in the in situ methods, we developed a procedure to separate cell types prior to analysis. The separation procedure has been verified with a study of HSV (1). This report presents data on the cellular localization of latent VZV, the frequency of latency, and the number of viral genomes present in latent cells.

A Phase I Study of the SMAC-Mimetic Birinapant in Adults with Refractory Solid Tumors or Lymphoma

“…The etiology of Bell's palsy following administration of birinapant is unclear. Bell's palsy may result from reactivation of VZV or HSV through an unknown mechanism (27,28). VZV DNA is sometimes present in the blood of patients who develop Bell's palsy and in some asymptomatic patients with altered immune function.…”

“…Varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA were evaluated as previously described (27,28).…”

Satellite glial cells in sensory ganglia: from form to function

“…Herpes simplex virus (HSV) causes painful blisters on the skin and mucous membranes, for example cold sores on the lips. It appears that in the latent phase the viruses are localized in the neurons of sensory ganglia, but rarely in SGCs [96]. However, SGCs may still have a role in this disease, as they are likely to form a barrier to the spread of the virus between infected and non-infected neurons [91,184].…”

Persistent Detection of Varicella-Zoster Virus DNA in a Previously Healthy Child after Severe Chickenpox

“…After acute infection, the virus develops latency in neuronal cells within trigeminal or dorsal root ganglia as shown by detection of VZV DNA at these sites (18,31,35,36). Unlike herpes simplex virus type 1 (HSV-1), viral protein expression has been demonstrated during latency, particularly the ORF63 transcript (8-10, 28, 29).…”