Synthesis and decay of varicella zoster virus transcripts

Azarkh, Yevgeniy; Dölken, Lars; Nagel, Maria A.; Gilden, Don; Cohrs, Randall J.

doi:10.1007/s13365-011-0029-2

Cited by 9 publications

(8 citation statements)

References 15 publications

(17 reference statements)

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“…The lack of VZV-induced CPE in human neurons is likely due to defective viral DNA replication or rapid degradation of VZV DNA. An absolute block in viral DNA replication in neurons is unlikely since late viral transcripts and their proteins, for which viral DNA replication is required, were detected (Azarkh et al, 2011; Baird et al, 2014; Grose et al, 2013; Yu et al, 2013). VZV DNA replication was ultimately sufficient to produce 31 PFU/culture, a level that would not have been detected above the ~10 9 input genomes.…”

Section: Discussionmentioning

confidence: 99%

Varicella zoster virus DNA does not accumulate in infected human neurons

Baird

Bowlin

et al. 2014

Virology

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Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. It is unclear why human neurons infected in vitro with VZV at low multiplicity of infection do not exhibit a cytopathic effect (CPE) even though all VZV genes are transcribed, VZV proteins from all kinetic classes are translated and minimal infectious virus is produced. Here, we show that the lack of VZV-induced CPE correlates with the low abundance of viral DNA.

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Section: Discussionmentioning

confidence: 99%

Varicella zoster virus DNA does not accumulate in infected human neurons

Baird

Bowlin

et al. 2014

Virology

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“…VZV was propagated by cocultivating infected cells with uninfected cells as described previously (27). Infected HFL cultures were harvested at the height of virus-induced cytopathic effect, usually at 3 days postinfection (dpi).…”

Section: Cells and Virusmentioning

confidence: 99%

Human Anti-Varicella-Zoster Virus (VZV) Recombinant Monoclonal Antibody Produced after Zostavax Immunization Recognizes the gH/gL Complex and Neutralizes VZV Infection

Birlea

Owens

Eshleman

et al. 2013

J Virol

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Varicella-zoster virus (VZV) is a ubiquitous, highly cell-associated, and exclusively human neurotropic alphaherpesvirus. VZV infection is initiated by membrane fusion, an event dependent in part on VZV glycoproteins gH and gL. Consistent with its location on the virus envelope, the gH/gL complex is a target of neutralizing antibodies produced after virus infection. One week after immunizing a 59-year-old VZV-seropositive man with Zostavax, we sorted his circulating blood plasma blasts and amplified expressed immunoglobulin variable domain sequences by single-cell PCR. Sequence analysis identified two plasma blast clones, one of which was used to construct a recombinant monoclonal antibody (rec-RC IgG). V aricella-zoster virus (VZV), the etiologic agent of varicella (chickenpox) and zoster (shingles), is an exclusively human pathogen and a member of the Herpesviridae family of enveloped DNA viruses. Herpesviruses cause both lytic and latent infections. Lytic infection requires membrane fusion, an event governed by a core complex consisting of conserved glycoproteins gB, gH, and gL. Along with membrane fusion, VZV gH and gL are also involved in virus egress and are essential for virus replication (1-4). In addition to mediating virus entry, VZV glycoproteins can traffic from infected cells to uninfected cells (5). VZV glycoproteins induce strong humoral immune responses both in naturally infected individuals and in varicella or zoster vaccine recipients (6-10). While VZV gE is the most immunogenic and predominant glycoprotein in VZV-infected cell membranes, antibodies to VZV gH are the major neutralizing antibodies (11-16). It is likely that neutralizing activity by the gH/gL complex effectively prevents cell-to-cell virus spread (5,(17)(18)(19)(20).Analysis of VZV attachment and membrane fusion requires highly specific neutralizing antibodies. Hybridoma cell lines and phage display libraries produce human anti-VZV gE and gH monoclonal antibodies (MAbs) that neutralize virus infection (21-24). Monoclonal antibodies that recognize the VZV gH/gL protein complex hold promise in therapies involving passive transfer of neutralizing VZV antibodies (15,16,25,26). Here we present a new method for constructing a recombinant human monoclonal anti-VZV antibody and show that this antibody detects a conformational epitope on the gH/gL complex and neutralizes virus. MATERIALS AND METHODS Cells and virus.Human lung fibroblast (HFL) and human embryonic kidney (HEK-EBNA 293) cells (American Type Culture Collection, Manassas, VA) were cultured in Dulbecco's modified Eagle's medium supplemented with 4 mM L-glutamine (DMEM; Sigma-Aldrich, St. Louis, MO) and 10% fetal bovine serum (FBS) (Atlanta Biologicals, Lawrenceville, GA). VZV was propagated by cocultivating infected cells with uninfected cells as described previously (27). Infected HFL cultures were harvested at the height of virus-induced cytopathic effect, usually at 3 days postinfection (dpi).Construction of recombinant antibody. Blood was collected 7 days after immunization...

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“…VZV DNA is found in sensory and autonomic ganglia along the entire neuraxis of infected individuals in a latent state that is largely restricted to neurons. Evidence from human cadaver dorsal root ganglia (DRG) suggest that VZV latency is associated with a limited lytic gene expression repertoire, in which mRNAs from some VZV genes (including open reading frames (ORFs) 4, 21, 29, 62, 63, 66) are expressed in some neurons in human DRG (Azarkh et al 2011; Gilden et al 2011; Kennedy and Cohrs 2010). Protein expression from the ORF 62, 63, and 66 genes has also been described (Cohrs et al 2003; Annunziato et al 1998; Lungu et al 1998; Zerboni et al 2010b), but this is controversial because of the recent indication that many antibodies used in such analyses also cross-react with human blood group A antigens (Zerboni et al 2011).…”

Section: Varicella Latency and Zostermentioning

confidence: 99%

Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models

Kinchington

Goins

2011

J. Neurovirol.

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Pain and post-herpetic neuralgia (PHN) are common and highly distressing complications of herpes zoster that remain a significant public health concern and in need of improved therapies. Zoster results from reactivation of the herpesvirus varicella zoster virus (VZV) from a neuronal latent state established at the primary infection (varicella). PHN occurs in some one fifth to one third of zoster cases with severity, incidence, and duration of pain increasing with rising patient age. While VZV reactivation and the ensuing ganglionic damage trigger the pain response, the mechanisms underlying protracted PHN are not understood, and the lack of an animal model of herpes zoster (reactivation) makes this issue more challenging. A recent preclinical rodent model has developed that opens up the potential to allow the exploration of the underlying mechanisms and treatments for VZV-induced pain. Rats inoculated with live cell-associated human VZV into the hind paw reliably demonstrate thermal hyperalgesia and mechanical allodynia for extended periods and then spontaneously recover. Dorsal root ganglia express a limited VZV gene subset, including the IE62 regulatory protein, and upregulate expression of markers suggesting a neuropathic pain state. The model has been used to investigate treatment modalities and aspects of pain signaling and is under investigation by the authors to delineate VZV genetics involved in the induction of pain. This article compares human zoster-associated pain and PHN to the pain indicators in the rat and poses important questions that, if answered, could be the basis for new treatments.

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Synthesis and decay of varicella zoster virus transcripts

Cited by 9 publications

References 15 publications

Varicella zoster virus DNA does not accumulate in infected human neurons

Varicella zoster virus DNA does not accumulate in infected human neurons

Human Anti-Varicella-Zoster Virus (VZV) Recombinant Monoclonal Antibody Produced after Zostavax Immunization Recognizes the gH/gL Complex and Neutralizes VZV Infection

Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models

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