scholarly journals Recent Issues in Varicella-Zoster Virus Latency

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2018
Author(s):  
Peter Kennedy ◽  
Trine Mogensen ◽  
Randall Cohrs
Keyword(s):  
Varicella Zoster Virus ◽  
Gene Transcription ◽  
Viral Gene ◽  
Special Focus ◽  
Inborn Errors ◽  
Varicella Zoster ◽  
Virus Latency ◽  
Human Herpes Virus ◽  
High Degree ◽  
Very High

Varicella-zoster virus (VZV) is a human herpes virus which causes varicella (chicken pox) as a primary infection, and, following a variable period of latency in neurons in the peripheral ganglia, may reactivate to cause herpes zoster (shingles) as well as a variety of neurological syndromes. In this overview we consider some recent issues in alphaherpesvirus latency with special focus on VZV ganglionic latency. A key question is the nature and extent of viral gene transcription during viral latency. While it is known that this is highly restricted, it is only recently that the very high degree of that restriction has been clarified, with both VZV gene 63-encoded transcripts and discovery of a novel VZV transcript (VLT) that maps antisense to the viral transactivator gene 61. It has also emerged in recent years that there is significant epigenetic regulation of VZV gene transcription, and the mechanisms underlying this are complex and being unraveled. The last few years has also seen an increased interest in the immunological aspects of VZV latency and reactivation, in particular from the perspective of inborn errors of host immunity that predispose to different VZV reactivation syndromes.

scholarly journals Transcriptomal analysis of varicella-zoster virus infection using long oligonucleotide-based microarrays

2005 ◽  
Vol 86 (10) ◽  
pp. 2673-2684 ◽  
Author(s):  
Peter G. E. Kennedy ◽  
Esther Grinfeld ◽  
Marie Craigon ◽  
Klemens Vierlinger ◽  
Douglas Roy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Varicella Zoster Virus ◽  
Gene Transcription ◽  
Spinal Ganglia ◽  
Viral Gene ◽  
Varicella Zoster Virus Infection ◽  
Global Pattern ◽  
Varicella Zoster ◽  
Viral Gene Transcription ◽  
Diagnostic Potential

Varicella-zoster virus (VZV) is a human herpes virus that causes varicella as a primary infection and herpes zoster following reactivation of the virus from a latent state in trigeminal and spinal ganglia. In order to study the global pattern of VZV gene transcription, VZV microarrays using 75-base oligomers to 71 VZV open reading frames (ORFs) were designed and validated. The long-oligonucleotide approach maximizes the stringency of detection and polarity of gene expression. To optimize sensitivity, microarrays were hybridized to target RNA and the extent of hybridization measured using resonance light scattering. Microarray data were normalized to a subset of invariant ranked host-encoded positive-control genes and the data subjected to robust formal statistical analysis. The programme of viral gene expression was determined for VZV (Dumas strain)-infected MeWo cells and SVG cells (an immortalized human astrocyte cell line) 72 h post-infection. Marked quantitative and qualitative differences in the viral transcriptome were observed between the two different cell types using the Dumas laboratory-adapted strain. Oligonucleotide-based VZV arrays have considerable promise as a valuable tool in the analysis of viral gene transcription during both lytic and latent infections, and the observed heterogeneity in the global pattern of viral gene transcription may also have diagnostic potential.

A mouse model for varicella-zoster virus latency

1993 ◽  
Vol 15 (2) ◽  
pp. 141-151 ◽  
Author(s):  
Zofia Wroblewska ◽  
Tibor Valyi-Nagy ◽  
Jessica Otte ◽  
Allan Dillner ◽  
Anita Jackson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Varicella Zoster Virus ◽  
Varicella Zoster ◽  
Virus Latency

scholarly journals Varicella-Zoster Virus IE63, a Major Viral Latency Protein, Is Required To Inhibit the Alpha Interferon-Induced Antiviral Response

2007 ◽  
Vol 81 (15) ◽  
pp. 7844-7851 ◽  
Author(s):  
Aruna P. N. Ambagala ◽  
Jeffrey I. Cohen
Keyword(s):  
Varicella Zoster Virus ◽  
Melanoma Cells ◽  
Alpha Interferon ◽  
Parental Virus ◽  
Initiation Factor ◽  
Viral Gene ◽  
Α Subunit ◽  
Varicella Zoster ◽  
In Cells ◽  
Hsv 1

ABSTRACT Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is the most abundant transcript expressed during latency in human sensory ganglia. VZV with ORF63 deleted is impaired for replication in melanoma cells and fibroblasts and for latency in rodents. We found that replication of the ORF63 deletion mutant is fully complemented in U2OS cells, which have been shown to complement the growth of herpes simplex virus type 1 (HSV-1) ICP0 mutants. Since HSV-1 ICP0 mutants are hypersensitive to alpha interferon (IFN-α), we examined the effect of IFN-α on VZV replication. Replication of the ORF63 mutant in melanoma cells was severely inhibited in the presence of IFN-α, in contrast to other VZV mutants that were similarly impaired for replication or to parental virus. The VZV ORF63 mutant was not hypersensitive to IFN-γ. IFN-α inhibited viral-gene expression in cells infected with the ORF63 mutant at a posttranscriptional level. Since IFN-α stimulates gene products that can phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF-2α) and inhibit translation, we determined whether cells infected with the ORF63 mutant had increased phosphorylation of eIF-2α compared with cells infected with parental virus. While phosphorylated eIF-2α was undetectable in uninfected cells or cells infected with parental virus, it was present in cells infected with the ORF63 mutant. Conversely, expression of IE63 (encoded by ORF63) in the absence of other viral proteins inhibited phosphorylation of eIF-2α. Since IFN-α has been shown to limit VZV replication in human skin xenografts, the ability of VZV IE63 to block the effects of the cytokine may play a critical role in VZV pathogenesis.

Varicella-Zoster Virus Latency in The Nervous System

1984 ◽  
pp. 93-102 ◽  
Author(s):  
Donald H. Gilden ◽  
Abbas Vafai ◽  
Yehuda Shtram ◽  
Yechiel Becker ◽  
Mary Devlin ◽  
...  
Keyword(s):  
Nervous System ◽  
Varicella Zoster Virus ◽  
Varicella Zoster ◽  
Virus Latency

scholarly journals Molecular Aspects of Varicella-Zoster Virus Latency

2018 ◽  
Author(s):  
Daniel P. Depledge ◽  
Tomohiko Sadaoka ◽  
Werner J. D. Ouwendijk
Keyword(s):  
Varicella Zoster Virus ◽  
Molecular Mechanisms ◽  
Neurological Complications ◽  
In Vitro Models ◽  
New Era ◽  
Varicella Zoster ◽  
Virus Latency ◽  
Technological Advances ◽  
Molecular Aspects

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.

scholarly journals Microarray Analysis of Host Cell Gene Transcription in Response to Varicella-Zoster Virus Infection of Human T Cells and Fibroblasts In Vitro and SCIDhu Skin Xenografts In Vivo

2003 ◽  
Vol 77 (2) ◽  
pp. 1268-1280 ◽  
Author(s):  
Jeremy O. Jones ◽  
Ann M. Arvin
Keyword(s):  
T Cells ◽  
Gene Regulation ◽  
Varicella Zoster Virus ◽  
Host Cell ◽  
Gene Transcription ◽  
Cell Types ◽  
Cellular Gene ◽  
Varicella Zoster ◽  
Human T Cells

ABSTRACT During primary infection, varicella-zoster virus (VZV) is spread via lymphocytes to skin, where it induces a rash and establishes latency in sensory ganglia. A live, attenuated varicella vaccine (vOka) was generated by using the VZV Oka strain (pOka), but the molecular basis for vOka attenuation remains unknown. Little is known concerning the effects of wild-type or attenuated VZV on cellular gene regulation in the host cells that are critical for pathogenesis. In this study, transcriptional profiles of primary human T cells and fibroblasts infected with VZV in cell culture were determined by using 40,000-spot human cDNA microarrays. Cellular gene transcription in human skin xenografts in SCID mice that were infected with VZV in vivo was also evaluated. The profiles of cellular gene transcripts that were induced or inhibited in infected human foreskin fibroblasts (HFFs), T cells, and skin in response to pOka and vOka infection were similar. However, significant alterations in cellular gene regulation were observed among the three differentiated human cell types that were examined, suggesting specific differences in the biological consequences of VZV infection related to the target cell. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time reverse transcription-PCR analysis of VZV-infected cells. Interestingly, the transcription of caspase 8 was found to be decreased in infected T cells but not in HFFs or skin, which may signify a tissue-specific antiapoptosis mechanism. The use of microarrays to demonstrate differences in effects on host cell genes in primary, biologically relevant cell types provides background information for experiments to link these various response phenotypes with mechanisms of VZV pathogenesis that are important for the natural course of human infection.

scholarly journals Varicella-zoster virus (VZV) origin of DNA replication oriS influences origin-dependent DNA replication and flanking gene transcription

Virology ◽  
2015 ◽  
Vol 481 ◽  
pp. 179-186 ◽  
Author(s):  
Mohamed I. Khalil ◽  
Marvin H. Sommer ◽  
John Hay ◽  
William T. Ruyechan ◽  
Ann M. Arvin
Keyword(s):  
Dna Replication ◽  
Varicella Zoster Virus ◽  
Gene Transcription ◽  
Varicella Zoster ◽  
Origin Of Dna Replication

scholarly journals Varicella-Zoster Virus Gene 66 Transcription and Translation in Latently Infected Human Ganglia

2003 ◽  
Vol 77 (12) ◽  
pp. 6660-6665 ◽  
Author(s):  
Randall J. Cohrs ◽  
Donald H. Gilden ◽  
Paul R. Kinchington ◽  
Esther Grinfeld ◽  
Peter G. E. Kennedy
Keyword(s):  
Varicella Zoster Virus ◽  
Gene Activation ◽  
Virus Production ◽  
Protein Product ◽  
Viral Gene ◽  
Reading Frame ◽  
Varicella Zoster ◽  
Virus Gene ◽  
Latently Infected

ABSTRACT Latent infection with varicella-zoster virus (VZV) is characterized by restricted virus gene expression and the absence of virus production. Of the ∼70 predicted VZV genes, only five (genes 4, 21, 29, 62, and 63) have been shown by multiple techniques to be transcribed during latency. IE62, the protein product of VZV gene 62, is the major immediate-early (IE) virus-encoded transactivator of viral gene transcription and plays a pivotal role in transactivating viral genes during lytic infection. The protein kinase (66-pk) encoded by VZV gene 66 phosphorylates IE62, resulting in cytoplasmic accumulation of IE62 that mitigates nuclear IE62-induced gene activation. Analysis of latently infected human trigeminal ganglia for 66-pk expression by reverse transcriptase-dependent nested PCR, including DNA sequence analysis, in situ hybridization, and immunohistochemistry, revealed VZV open reading frame 66 to be a previously unrecognized latently expressed virus gene and suggests that prevention of IE62 import to the nucleus by VZV 66-pk phosphorylation is one possible mechanism by which VZV latency is maintained.

scholarly journals Varicella-Zoster Virus Transfer to Skin by T Cells and Modulation of Viral Replication by Epidermal Cell Interferon-α

2004 ◽  
Vol 200 (7) ◽  
pp. 917-925 ◽  
Author(s):  
Chia-Chi Ku ◽  
Leigh Zerboni ◽  
Hideki Ito ◽  
Brad S. Graham ◽  
Mark Wallace ◽  
...  
Keyword(s):  
T Cells ◽  
Varicella Zoster Virus ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Severe Combined Immunodeficiency ◽  
Immune Surveillance ◽  
Epidermal Cells ◽  
Viral Gene ◽  
Interferon Α ◽  
Varicella Zoster

Primary infection with varicella-zoster virus (VZV) causes the characteristic syndrome of varicella, or chickenpox. Experiments in severe combined immunodeficiency mice with human skin grafts (SCIDhu mice) indicate that VZV infection of T cells can mediate transfer of infectious virus to skin. VZV-infected T cells reached epithelial sites of replication within 24 h after entering the circulation. Memory CD4+ T cells were the predominant population recovered from skin in SCIDhu mice given uninfected or infected mononuclear cells, suggesting that immune surveillance by memory T cells may facilitate VZV transfer. The increased susceptibility of memory T cells to VZV infection may further enhance their role in VZV pathogenesis. During VZV skin infection, viral gene products down-regulated interferon-α to permit focal replication, whereas adjacent epidermal cells mounted a potent interferon-α response against cell–cell spread. Interleukin-1α, although activated in VZV-infected cells, did not trigger expression of endothelial adhesion molecules, thereby avoiding early recruitment of inflammatory cells. The prolonged varicella incubation period appears to represent the time required for VZV to overcome antiviral responses of epidermal cells and generate vesicles at the skin surface. Modulation of VZV replication by cutaneous innate immunity may avoid an incapacitating infection of the host that would limit opportunities for VZV transmission.

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