Presence, Distribution and Spread of Productive Varicella Zoster Virus Infection in Nervous Tissues

Abstract

Nervous tissue lesions were retrospectively studied for detection of productive varicella zoster virus (VZV) infection in 33 autopsied cases, including 19 herpes zoster (HZ) (10 trigeminal, nine spinal) and 14 cases of nodular brainstem encephalitis without HZ. Immunocytochemistry for VZV antigens and in situ hybridization with a biotinylated VZV DNA probe were used on formol-fixed paraffin sections. Peripheral and central nervous system, skin and striated muscle were investigated in serial sections; available tissue blocks, however, varied between cases. Varicella zoster virus production (both antigen and DNA) in nervous tissue was found in HZ cases but only of short survival after a rash of up to 7 wks (eight out of 12 patients). Varicella zoster virus was visualized in nerve cells, glial cells, Schwann cells and blood vessels. In the central nervous system (CNS), VZV was detected in trigeminal nuclei (one out of 10 brains) or disseminated nodular brainstem lesions (one out of 10 brains), in subependymal microvessels (one out of 10 brains) or vasculitic arteries (two out of 19 brains or spinal cords). In the peripheral nervous system (PNS), VZV (DNA and antigen) was found in neurons and satellite cells of sensory ganglia (four out of seven cases with sampling of ganglia), and in damaged nerve fibres including a muscle nerve in one case; myositis with VZV in affected muscle fibres was found in the latter case. In nodular brainstem encephalitis, one case contained VZV within nodular lesions. We conclude that (i) VZV neural spread is suggested by detectable virus in ganglia, nerve fibres and CNS target nuclei; (ii) haematogenous spread of VZV is suggested by detection of virus in CNS microvessels and in disseminated brainstem encephalitis; (iii) VZV myositis may occur in zosteric myotomes; and (iv) VZV is a possible agent in nodular brainstem encephalitis.

Varicella-Zoster Virus-Specific Enzyme-Linked Immunospot Assay Responses and Zoster-Associated Pain in Herpes Zoster Subjects

“…Additionally, levels of pain in the acute phase were similar in younger and older patients. These observations are consistent with clinical evidence that VZV-induced neuronal damage occurs early in HZ, as reflected in prodromal signs and symptoms (5) and significant ganglionitis and VZV antigen found in the sensory ganglion very early after HZ onset (4,6,16). These findings suggest that the zoster vaccine protects older vaccinees shortly after administration, which is consistent with observations that a protective effect was noted within the 30-day postvaccination period during the definitive trial of the current vaccine (13).…”

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

“…Ongoing viral replication was also suggested by Schmidbauer et al (29), who detected viral antigens (gH and nucleoprotein) and VZV DNA in ganglia from 7 patients up to 7 weeks after the onset of the herpes zoster rash. Interestingly, as in our study, they only identified viral antigens in necrotic regions of the ganglia (29). We have previously shown that VZV-infected neurons expressing IE63 are resistant to apoptosis (7).…”

“…Previous histological studies of ganglia from patients with herpes zoster close to the time of death noted necrosis in part or the whole of the ganglia, with some hemorrhage and lymphocytic infiltration (27)(28)(29)(30)(31)(32). Some cases also showed vascular involvement with perivascular lymphocytic cuffing and thrombosis noted (28,31).…”

Cervical Myelopathy following Lumbar Herpes zoster

“…Neurologic symptoms usually develop within days to weeks after the rash and present a chronic progression [1, 2], while a remitting-exacerbating course has been rarely described [3]. This clinical profile is supported by pathological studies, disclosing necrotizing inflammatory abnormalities and demyelination lesions, mainly involving the posterior horns and the dorsal columns [1, 2, 4]. The pathogenesis is not entirely understood.…”