scholarly journals BAG3, a Host Cochaperone, Facilitates Varicella-Zoster Virus Replication

2007 ◽  
Vol 81 (14) ◽  
pp. 7491-7503 ◽  
Author(s):  
Christos A. Kyratsous ◽  
Saul J. Silverstein
Keyword(s):  
Varicella Zoster Virus ◽  
Virus Replication ◽  
Latent Infection ◽  
Dna Binding Protein ◽  
Lytic Replication ◽  
Regulatory Proteins ◽  
Varicella Zoster ◽  
Associated Proteins ◽  
Hsp90 Activity ◽  
Interfering Rna

ABSTRACT Varicella-zoster virus (VZV) establishes a lifelong latent infection in the dorsal root ganglia of the host. During latency, a subset of virus-encoded regulatory proteins is detected; however, they are excluded from the nucleus. ORF29p, a single-stranded DNA binding protein, is one of these latency-associated proteins. We searched for cell proteins that interact with ORF29p and identified BAG3. BAG3, Hsp70/Hsc70, and Hsp90 colocalize with ORF29p in nuclear transcription/replication factories during lytic replication of VZV. Pharmacological intercession of Hsp90 activity with ansamycin antibiotics or depletion of BAG3 by small interfering RNA results in inhibition of virus replication. Replication in BAG3-depleted cell lines is restored by complementation with exogenous BAG3. Alteration of host chaperone activity provides a novel means of regulating virus replication.

scholarly journals Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency

1998 ◽  
Vol 95 (12) ◽  
pp. 7080-7085 ◽  
Author(s):  
O. Lungu ◽  
C. A. Panagiotidis ◽  
P. W. Annunziato ◽  
A. A. Gershon ◽  
S. J. Silverstein
Keyword(s):  
Varicella Zoster Virus ◽  
Intracellular Localization ◽  
Regulatory Proteins ◽  
Varicella Zoster

scholarly journals Inhibition of varicella-zoster virus replication by an inhibitor of protein myristoylation

1993 ◽  
Vol 74 (6) ◽  
pp. 1181-1184 ◽  
Author(s):  
D. R. Harper ◽  
R. L. Gilbert ◽  
C. Blunt ◽  
R. A. J. McIlhinney
Keyword(s):  
Varicella Zoster Virus ◽  
Virus Replication ◽  
Varicella Zoster ◽  
Protein Myristoylation

Resveratrol inhibition of varicella-zoster virus replication in vitro

2006 ◽  
Vol 72 (3) ◽  
pp. 171-177 ◽  
Author(s):  
John J. Docherty ◽  
Thomas J. Sweet ◽  
Erin Bailey ◽  
Seth A. Faith ◽  
Tristan Booth
Keyword(s):  
Varicella Zoster Virus ◽  
Virus Replication ◽  
Varicella Zoster

scholarly journals Varicella-Zoster Virus ORF47 Protein Kinase, Which Is Required for Replication in Human T Cells, and ORF66 Protein Kinase, Which Is Expressed during Latency, Are Dispensable for Establishment of Latency

2003 ◽  
Vol 77 (20) ◽  
pp. 11180-11185 ◽  
Author(s):  
Hitoshi Sato ◽  
Lesley Pesnicak ◽  
Jeffrey I. Cohen
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Varicella Zoster Virus ◽  
Latent Infection ◽  
Viral Proteins ◽  
Parental Virus ◽  
Reading Frame ◽  
Varicella Zoster ◽  
Human T Cells ◽  
Simplex Virus

ABSTRACT Varicella-zoster virus (VZV) results in a lifelong latent infection in human sensory and cranial nerve ganglia after primary infection. VZV open reading frame 47 (ORF47) and ORF66 encode protein kinases that phosphorylate several viral proteins, including VZV glycoprotein gE and ORF32, ORF62, and ORF63 proteins. Here we show that the ORF47 protein kinase also phosphorylates gI. While ORF47 is essential for virus replication in human T cells and skin, we found the gene to be dispensable for establishment of latent infection in dorsal root ganglia of rodents. ORF66 protein is expressed during latency. Rodents infected with VZV unable to express ORF66 developed latent infection at a rate similar to that for the parental virus. ORF63 transcripts, a hallmark of VZV latency, were also detected in similar numbers of animals infected with the ORF47 and ORF66 mutants and with the parental virus. VZV mutants unable to express four of the six genes that do not have herpes simplex virus (HSV) homologs (ORFs 1, 13, 32, 57) were also unimpaired for establishment of latency. While a truncated HSV VP16 mutant was previously reported to be unable to establish latency in a mouse model, we found that VZV with a deletion of ORF10, the homolog of HSV VP16, was dispensable for establishment of latency. Thus, seven genes, including one expressed during latency, are dispensable for establishing latent VZV infection.

scholarly journals Epigenetic Regulation of Varicella-Zoster Virus Open Reading Frames 62 and 63 in Latently Infected Human Trigeminal Ganglia

2006 ◽  
Vol 80 (10) ◽  
pp. 4921-4926 ◽  
Author(s):  
Lee Gary ◽  
Donald H. Gilden ◽  
Randall J. Cohrs
Keyword(s):  
Varicella Zoster Virus ◽  
Chromatin Immunoprecipitation ◽  
Latent Infection ◽  
Open Reading Frames ◽  
Trigeminal Ganglia ◽  
Varicella Zoster ◽  
Glycoprotein C ◽  
Latently Infected ◽  
Human Chromosome 4 ◽  
Reading Frames

ABSTRACT Open reading frames (ORFs) 21, 29, 62, 63, and 66 of varicella-zoster virus (VZV) are transcribed during latency in human ganglia. ORF 63 is the most frequently expressed gene, and ORF 62 encodes a transcriptional activator. The mechanisms regulating the expression of these genes are not well understood, although analyses of other alphaherpesviruses indicate a role for chromatin in virus gene regulation during latent infection. Using chromatin immunoprecipitation (ChIP) assays to analyze the euchromatic state of ORFs 62 and 63 compared to the centromere from human chromosome 4 (heterochromatic) and the human glyceraldehyde-3-phosphate dehydrogenase promoter (euchromatic), we show that the promoters of ORFs 62 and 63 are associated with the histone protein H3K9(Ac) and thus maintained in a euchromatic state during latency. Conversely, the promoters of ORF 36 (thymidine kinase) and ORF 14 (glycoprotein C), genes expressed during lytic but not latent infection, were not enriched in the fraction of latently infected ganglia that bound to anti-H3K9(Ac) antibody. A ChIP assay using productively infected MeWo cells revealed that VZV ORFs 62, 63, 36, and 14 are all euchromatic. Together, these data indicate that the expression of the two latency-related VZV genes, ORFs 62 and 63, is regulated epigenetically through chromatin structure.

scholarly journals Amylin, Aβ42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells

2020 ◽  
Author(s):  
Andrew N Bubak ◽  
Cheryl Beseler ◽  
Christina N Como ◽  
Christina M Coughlan ◽  
Noah R Johnson ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Varicella Zoster Virus ◽  
Amyloid Fibrils ◽  
Central Nervous System Infection ◽  
Amyloid Deposition ◽  
Amyloid Formation ◽  
Varicella Zoster ◽  
Arterial Inflammation ◽  
Amyloidogenic Peptides ◽  
Interfering Rna

Abstract Background Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. Methods Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin’s function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. Results Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. Conclusions VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

Honeysuckle-derived microRNA2911 directly inhibits varicella-zoster virus replication by targeting IE62 gene

2019 ◽  
Vol 25 (4) ◽  
pp. 457-463 ◽  
Author(s):  
Ying Huang ◽  
Huabo Liu ◽  
Xinlei Sun ◽  
Meng Ding ◽  
Gaojian Tao ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Virus Replication ◽  
Varicella Zoster

scholarly journals Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5′ untranslated region and participates in virus replication

2008 ◽  
Vol 89 (10) ◽  
pp. 2540-2549 ◽  
Author(s):  
Jing-Yi Lin ◽  
Mei-Ling Li ◽  
Peng-Nien Huang ◽  
Kun-Yi Chien ◽  
Jim-Tong Horng ◽  
...  
Keyword(s):  
Virus Replication ◽  
Untranslated Region ◽  
Enterovirus 71 ◽  
Neurological Complications ◽  
Negative Control ◽  
Hnrnp K ◽  
Associated Proteins ◽  
Interaction Regions ◽  
Nuclear Ribonucleoprotein ◽  
Interfering Rna

Enterovirus 71 (EV71) is a picornavirus that can cause severe neurological complications in children. Like other picornaviruses, the genomic RNA of EV71 contains a long 5′ untranslated region (UTR). Cellular proteins interact with the EV71 5′ UTR, and these interactions are important for virus replication. Using an RNA pull-down assay and proteomics approaches, this study identified the heterogeneous nuclear ribonucleoprotein K (hnRNP K) as one of the EV71 5′ UTR-associated proteins. The interaction between hnRNP K and the 5′ UTR was further confirmed by mapping the interaction regions to stem–loops I–II and IV in the 5′ UTR. During EV71 infection, hnRNP K was enriched in the cytoplasm where virus replication occurs, whereas hnRNP K was localized in the nucleus in mock-infected cells. Viral yields were found to be significantly lower in hnRNP K knockdown cells and viral RNA synthesis was delayed in hnRNP K knockdown cells in comparison with negative-control cells treated with small interfering RNA. These results suggest that hnRNP K interacts with the EV71 5′ UTR and participates in virus replication.

scholarly journals Components of Nuclear Domain 10 Bodies Regulate Varicella-Zoster Virus Replication

2009 ◽  
Vol 83 (9) ◽  
pp. 4262-4274 ◽  
Author(s):  
Christos A. Kyratsous ◽  
Saul J. Silverstein
Keyword(s):  
Varicella Zoster Virus ◽  
Virus Replication ◽  
Control Cell ◽  
Host Cells ◽  
Virus Protein ◽  
Protein Accumulation ◽  
Dna Virus ◽  
Varicella Zoster ◽  
Early Protein ◽  
Nuclear Domains

ABSTRACT PML, Sp100, and Daxx are proteins that normally reside within nuclear domains 10 (ND10s). They associate with DNA virus genomes and repress the very early stages of the DNA virus replication cycle. Virus-encoded proteins counteract this innate antiviral response. ICP0, a herpes simplex virus (HSV) immediate-early protein, is necessary and sufficient to dissociate ND10s and target their two major components, PML and Sp100, for proteasomal degradation. In this report, we show that ORF61p, the varicella-zoster virus (VZV) ortholog of ICP0, does not degrade PML and alters Sp100 levels only slightly. Furthermore, we demonstrate that other virus proteins cannot substitute for this lack of function during infection. By using short interfering RNAs, we depleted PML, Sp100, and Daxx and studied their roles in plaquing efficiency, virus protein accumulation, infectious-center titer, and virus spread. The results of these studies show that components of ND10s can accelerate VZV replication but do not ultimately control cell-associated virus titers. We conclude that while both ICP0 and ORF61p activate virus gene expression, they modulate host innate repression mechanisms in two different ways. As a result, HSV and VZV commandeer their host cells by distinct mechanisms to ensure their replication and spread.

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