Latent Varicella–Zoster Viral DNA in Human Trigeminal and Thoracic Ganglia

Mahalingam, Ravi; Wellish, Mary; Wolf, Walter J.; Dueland, Aud Nome; Cohrs, Randall J.; Vafai, Abbas; Gilden, Donald H.

doi:10.1056/nejm199009063231002

Cited by 241 publications

(106 citation statements)

References 17 publications

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“…The observation that IE proteins were expressed in neural cells in the NOD-SCID mouse-human neural cell model while gE synthesis was reduced serves to validate reports about VZV gene transcription and translation in neural cells within human sensory ganglia obtained at autopsy and in animal models (2,4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Conclusions from autopsy specimens have been questioned because VZV gene expression might be triggered during the time required to obtain tissues, and infection of nonhuman neural cells in animals may not reproduce the VZV pathogenesis in the human host accurately.…”

Section: Discussionmentioning

confidence: 68%

“…Herpes simplex virus 1 produces latency-associated antisense mRNA transcripts (LATs) in neuronal cell nuclei, and viral proteins are not detected in human autopsy specimens or animal models of persistent infection (6). In contrast, VZV has no LAT sequence, and transcription or translation of VZV genes encoding the IE major transactivating protein, IE62, the IE63 coregulatory protein, and ORFs 4, 21, 29, 40, and 66 has been reported in ganglia (2,4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

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confidence: 99%

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Varicella-zoster virus infection of human neural cells in vivo

Baiker

Fabel

Cozzio

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Varicella-zoster virus (VZV) establishes latency in sensory ganglia and causes herpes zoster upon reactivation. These investigations in a nonobese diabetic severe combined immunodeficient mousehuman neural cell model showed that VZV infected both neurons and glial cells and spread efficiently from cell to cell in vivo. Neural cell morphology and protein synthesis were preserved, in contrast to destruction of epithelial cells by VZV. Expression of VZV genes in neural cells was characterized by nuclear retention of the major viral transactivating protein and a block in synthesis of the predominant envelope glycoprotein. The attenuated VZV vaccine strain retained infectivity for neurons and glial cells in vivo. VZV gene expression in differentiated human neural cells in vivo differs from neural infection by herpes simplex virus, which is characterized by latency-associated transcripts, and from lytic VZV replication in skin. The chimeric nonobese diabetic severe combined immunodeficient mouse model may be useful for investigating other neurotropic human viruses.

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Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

Varicella-zoster virus infection of human neural cells in vivo

Baiker

Fabel

Cozzio

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…New formulations of the vaccine with high titres and increased stability of the virus, like the vaccine used for these studies, raise the response rate in the vaccinees without an increase in the number of serious adverse events (10,11). Additional concerns were raised by the persistence and reactivation of wild type VZV in elderly or immunodepressed patients (16,17). It has been shown that the OKA strain persists in vaccinees and that it can be reactivated in immunocompromised or healthy hosts; however, zoster rates were significantly lower and milder than in nonvaccinees (2).…”

Section: Discussionmentioning

confidence: 99%

Reactogenicity to a Live Attenuated Varicella Vaccine in Canadian Children

Díaz‐Mitoma

Halperin²,

Scheifele³

2000

Canadian Journal of Infectious Diseases and Medical Microbiolog

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OBJECTIVE:To assess the reactogenicity and safety of a thermostable, high titre, varicella vaccine in healthy infants and children. DESIGN: Open study of 505 children monitored for 42 days after vaccination. SETTING: Three urban Canadian centres (Halifax, Ottawa and Vancouver). PARTICIPANTS: 505 healthy children one to 12 years of age were enrolled and 504 completed the study. All were susceptible to varicella by history. INTERVENTIONS: All participants received one dose of live attenuated varicella vaccine (1×10 4.5 plaque forming units/dose) subcutaneously. MAIN OUTCOME MEASURES: The children were monitored from the day of vaccine administration (day 0) until day 42. All local and general symptoms and signs were recorded on diary cards by the patients' parents, who were encouraged to fill in the cards on days 2 to 3 and 18 to 24 via telephone calls from study personnel. RESULTS: Most of the symptoms noted after vaccine administration were mild and transient, and all resolved within the respective follow-up periods. Injection site symptoms included pain (17.5%, 13.9% and 30.4% in centres 1, 2 and 3 respectively), redness (21.1%, 32.1% and 48.8%) and swelling (7%, 10.3% and 29.2%). The general symptoms reported were fever 37.5°C or higher (3.5%, 4.8% and 3.0%) and varicella-like rashes (6.4%, 2.4% and 0%). Two subjects had severe symptoms (one with cervical lymphadenopathy, and one with a fever higher than 39°C) probably related to vaccine administration. No serious adverse events were reported during the entire study. CONCLUSION: The vaccine was well tolerated. I nfection by varicella zoster virus (VZV) usually results in benign disease in children. However, complications such as pneumonia, encephalitis and bacterial superinfection of the skin lesions (1,2) occur in some patients, mainly in adolescents and adults, and in immunocompromised children (1,2). In addition, children born to nonimmune mothers who contract varicella during pregnancy can develop congenital varicella syndrome (1,3), with limb hypoplasia and central nervous system damage.A live varicella vaccine was developed in Japan in 1974 (4) using the OKA strain of the virus. The original wild type virus was isolated from a boy with natural varicella, and then attenuated by passages through human and guinea pig embryonic cells, and two human diploid cell lines, WI-38 and MRC-5 (4,5). The vaccine strain obtained after this treatment has different thermosensitivity and host range spectrum than the wild type virus (6). Additionally, it can be easily differentiated from wild type strains currently circulating in North America by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) testing (6,7).All OKA varicella vaccine production lots are derived directly from a working seed lot (8), following the World Health Organization guidelines (9). Many clinical trials have demonstrated that this strain is safe and immunogenic (2,5,10,11). The vaccine produced by SmithKline Beecham Biologicals (Rixensart, Belgium), VARILRIX, was firs...

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“…Primary infection, usually in childhood, causes varicella (chickenpox), after which virus become latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis (1). As cellmediated immunity to VZV declines with advancing age and immunosuppression, VZV reactivates to produce herpes zoster (shingles), frequently complicated by postherpetic neuralgia (radicular pain that persists long after the disappearance of rash).…”

Section: Introductionmentioning

confidence: 99%

Varicella Zoster Virus: A Common Cause of Stroke in Children and Adults

Amlie‐Lefond

Gilden

2016

Journal of Stroke and Cerebrovascular Diseases

101

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Background-Varicella zoster virus (VZV) is a neurotropic exclusively human herpesvirus. Primary infection causes varicella (chickenpox), after which virus become latent in ganglionic neurons along the entire neuraxis. As cell-mediated immunity to VZV declines with advancing age and immunosuppression, VZV reactivates to produce zoster (shingles). One of the most serious complications of zoster is VZV vasculopathy.

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Latent Varicella–Zoster Viral DNA in Human Trigeminal and Thoracic Ganglia

Abstract: 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.

Cited by 241 publications

References 17 publications

Varicella-zoster virus infection of human neural cells in vivo

Varicella-zoster virus infection of human neural cells in vivo

Reactogenicity to a Live Attenuated Varicella Vaccine in Canadian Children

Varicella Zoster Virus: A Common Cause of Stroke in Children and Adults

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