Fatal varicella due to the vaccine-strain varicella-zoster virus

Leung, Jessica; Siegel, Subhadra; Jones, James F.; Schulte, Cynthia; Blog, Debra; Schmid, Daniela; Bialek, Stephanie R.; Marin, Mona

doi:10.4161/hv.26200

Cited by 47 publications

(27 citation statements)

References 29 publications

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“…33,34 Along these lines, prospective studies are needed to determine whether patients with severe asthma, particularly steroid-dependent asthma, or with other severe atopic conditions are at an increased risk of breakthrough varicella infection or other vaccine-preventable diseases.…”

Section: Discussionmentioning

confidence: 99%

Asthma and risk of breakthrough varicella infection in children

Umaretiya

Swanson

Kwon

et al. 2016

allergy asthma proc

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Section: Discussionmentioning

confidence: 99%

Asthma and risk of breakthrough varicella infection in children

Umaretiya

Swanson

Kwon

et al. 2016

allergy asthma proc

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“…Of some concern are reports that the live vaccine can cause disease in healthy (66)(67)(68)(69)(70)(71) and immunocompromised (72)(73)(74) individuals. A case of zoster that later disseminated due to an acyclovir-resistant Oka strain has been reported (75).…”

Section: Discussionmentioning

confidence: 99%

The Varicella-Zoster Virus Portal Protein Is Essential for Cleavage and Packaging of Viral DNA

Visalli

House

Selariu

et al. 2014

J Virol

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The varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87-kDa monomer that oligomerizes to form the VZV portal protein, pORF54. pORF54 was hypothesized to perform a function similar to that of a previously described herpes simplex virus 1 (HSV-1) homolog, pUL6. pUL6 and the associated viral terminase are required for processing of concatemeric viral DNA and packaging of individual viral genomes into preformed capsids. In this report, we describe two VZV bacterial artificial chromosome (BAC) constructs with ORF54 gene deletions, ⌬54L (full ORF deletion) and ⌬54S (partial internal deletion). The full deletion of ORF54 likely disrupted essential adjacent genes (ORF53 and ORF55) and therefore could not be complemented on an ORF54-expressing cell line (ARPE54). In contrast, ⌬54S was successfully propagated in ARPE54 cells but failed to replicate in parental, noncomplementing ARPE19 cells. Transmission electron microscopy confirmed the presence of only empty VZV capsids in ⌬54S-infected ARPE19 cell nuclei. Similar to the HSV-1 genome, the VZV genome is composed of a unique long region (U L ) and a unique short region (U S ) flanked by inverted repeats. DNA from cells infected with parental VZV (VZV LUC strain) contained the predicted U L and U S termini, whereas cells infected with ⌬54S contained neither. This result demonstrates that ⌬54S is not able to process and package viral DNA, thus making pORF54 an excellent chemotherapeutic target. In addition, the utility of BAC constructs ⌬54L and ⌬54S as tools for the isolation of site-directed ORF54 mutants was demonstrated by recombineering single-nucleotide changes within ORF54 that conferred resistance to VZV-specific portal protein inhibitors. IMPORTANCE Antivirals with novel mechanisms of action would provide additional therapeutic options to treat human herpesvirus infections.Proteins involved in the herpesviral DNA encapsidation process have become promising antiviral targets. Previously, we described a series of N-␣-methylbenzyl-N=-aryl thiourea analogs that target the VZV portal protein (pORF54) and prevent viral replication in vitro. To better understand the mechanism of action of these compounds, it is important to define the structural and functional characteristics of the VZV portal protein. In contrast to HSV, no VZV mutants have been described for any of the seven essential DNA encapsidation genes. The VZV ORF54 deletion mutant described in this study represents the first VZV encapsidation mutant reported to date. We demonstrate that the deletion mutant can serve as a platform for the isolation of portal mutants via recombineering and provide a strategy for more in-depth studies of VZV portal structure and function.H erpesvirus DNA encapsidation is understood only in general terms. The mechanistic events and the function(s) of the proteins involved are still under investigation. During viral replication, progeny DNA genomes are synthesized in the nucleus as long, branched head-to-tail concatemers. The capsid proteins are synt...

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“…These included initially unrecognized forms of severe immunodeficiency disease, RAG 2 deficiency and ADA deficiency. 51–54 Severe adverse reactions after vaccination but with recovery after antiviral therapy were observed in a child with undiagnosed HIV infection, 55 DOCK 2 deficiency, DOCK 8 deficiency with hyper-IgE and STAT mutations; some of these children also had functional abnormalities of natural killer (NK) cells. 56–60 Rarely, children with severe varicella who only lacked natural killer cells (NK) have been described, further implicating innate immunity in host defense against VZV.…”

Section: Immunity To Vzvmentioning

confidence: 99%

Is chickenpox so bad, what do we know about immunity to varicella zoster virus, and what does it tell us about the future?

Gershon

2017

Journal of Infection

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Summary Varicella and zoster continue to cause significant morbidity and even mortality in children and adults. Complications include bacterial superinfection, central nervous system manifestations such as meningitis, encephalitis, and cerebellar ataxia, and pain syndromes especially post herpetic neuralgia. Many developed countries but not all, are now administering live attenuated varicella vaccine routinely, with a decrease in the incidence of disease, providing personal and herd immunity. There is some controversy, however, in some countries concerning whether a decrease in the circulation of wild type virus will result in loss of immunity to VZV in persons who have already had varicella. This manuscript reviews the complications of varicella and zoster in detail, the reasons for development of vaccines against these diseases, complications of vaccinations, and mechanisms by which immunity to this virus develops and is maintained. There are strong indications that the best way to control disease and spread of this virus is by vaccination against both.

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Fatal varicella due to the vaccine-strain varicella-zoster virus

Cited by 47 publications

References 29 publications

Asthma and risk of breakthrough varicella infection in children

Asthma and risk of breakthrough varicella infection in children

The Varicella-Zoster Virus Portal Protein Is Essential for Cleavage and Packaging of Viral DNA

Is chickenpox so bad, what do we know about immunity to varicella zoster virus, and what does it tell us about the future?

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