scholarly journals Cytotoxicity of glioblastoma cells mediated ex vivo by varicella-zoster virus-specific T cells

2011 ◽  
Vol 17 (5) ◽  
pp. 448-454 ◽  
Author(s):  
Jennifer Canniff ◽  
Andrew M. Donson ◽  
Nicholas K. Foreman ◽  
Adriana Weinberg
Keyword(s):  
T Cells ◽  
Varicella Zoster Virus ◽  
Ex Vivo ◽  
Glioblastoma Cells ◽  
Varicella Zoster

scholarly journals Persistent High Frequencies of Varicella-Zoster Virus ORF4 Protein-Specific CD4+ T Cells after Primary Infection

2006 ◽  
Vol 80 (19) ◽  
pp. 9772-9778 ◽  
Author(s):  
Louise Jones ◽  
Antony P. Black ◽  
Gathsaurie N. Malavige ◽  
Graham S. Ogg
Keyword(s):  
T Cells ◽  
Varicella Zoster Virus ◽  
Peripheral Blood ◽  
Primary Infection ◽  
Ex Vivo ◽  
High Frequencies ◽  
Varicella Zoster ◽  
Early Protein ◽  
Orf4 Protein ◽  
Ifn Γ

ABSTRACT Open reading frame 4 (ORF4) of varicella-zoster virus (VZV) encodes an immediate-early protein that is believed to be important for viral infectivity and establishing latency. Evidence suggests that VZV-specific T cells are crucial in the control of viral replication, but there are no data addressing the existence of potential ORF4 protein-specific CD4+ T cells. We tested the hypothesis that VZV ORF4 protein-specific CD4+ T cells could be identified and characterized within the peripheral blood of healthy immune donors following primary infection. Gamma interferon (IFN-γ) immunosorbent assays were used to screen peripheral blood mononuclear cells obtained from healthy seropositive donors for responses to overlapping ORF4 peptides, viral lysate, and live vaccine. High frequencies of ORF4 protein-specific T cells were detected ex vivo in individuals up to 52 years after primary infection. Several immunogenic regions of the ORF4 protein were identified, including a commonly recognized epitope which was restricted through HLA-DRB1*07. Total ORF4 protein-specific responses comprised 19.7% and 20.7% of the total lysate and vaccine responses, respectively, and were dominated by CD4+ T cells. Indeed, CD4+ T cells were found to dominate the overall virus-specific IFN-γ cellular immune response both ex vivo and after expansion in vitro. In summary, we have identified an ORF4 protein as a novel target antigen for persistent VZV-specific CD4+ T cells, with implications for disease pathogenesis and future vaccine development.

scholarly journals Identification of Varicella-Zoster Virus-Specific CD8 T Cells in Patients after T-Cell-Depleted Allogeneic Stem Cell Transplantation

2009 ◽  
Vol 83 (14) ◽  
pp. 7361-7364 ◽  
Author(s):  
Pim L. J. van der Heiden ◽  
Renate de Boer ◽  
Dirk M. van der Steen ◽  
Michel G. D. Kester ◽  
Menno W. A. G. van der Hoorn ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Varicella Zoster Virus ◽  
Cell Transplantation ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Binding Capacity ◽  
Varicella Zoster ◽  
Major Histocompatibility Complexes

ABSTRACT To study the role of CD8 T cells in the control of varicella-zoster virus (VZV) reactivation, we developed multimeric major histocompatibility complexes to identify VZV-specific CD8 T cells. Potential HLA-A2 binding peptides from the putative immediate-early 62 protein (IE62) of VZV were tested for binding, and peptides with sufficient binding capacity were used to generate pentamers. Patients with VZV reactivation following stem cell transplantation were screened with these pentamers, leading to the identification of the first validated class I-restricted epitope of VZV. In 42% of HLA-A2 patients following VZV reactivation, these IE62-ALW-A2 T cells could be detected ex vivo.

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 Replication of Varicella-Zoster Virus in Human Skin Organ Culture

2005 ◽  
Vol 79 (17) ◽  
pp. 11501-11506 ◽  
Author(s):  
Shannon L. Taylor ◽  
Jennifer F. Moffat
Keyword(s):  
Organ Culture ◽  
Varicella Zoster Virus ◽  
Ex Vivo ◽  
Plaque Assay ◽  
Rodent Models ◽  
Fetal Skin ◽  
Varicella Zoster ◽  
Transmission Electron ◽  
Models Of Disease ◽  
Skin Organ Culture

ABSTRACT Varicella-zoster virus (VZV) infection is restricted to humans, which hinders studies of its pathogenesis in rodent models of disease. To facilitate the study of VZV skin tropism, we developed an ex vivo system using human fetal skin organ culture (SOC). VZV replication was analyzed by plaque assay, transmission electron microscopy, and histology. The yield of infectious VZV from SOC increased ∼100-fold over 6 days, virions were abundant, and lesions developed that contained VZV antigens and resembled varicella and zoster lesions. The SOC system for VZV replication has applications for testing virus mutants and antiviral drugs.

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 The Characterization of Varicella Zoster Virus–Specific T Cells in Skin and Blood during Aging

2015 ◽  
Vol 135 (7) ◽  
pp. 1752-1762 ◽  
Author(s):  
Milica Vukmanovic-Stejic ◽  
Daisy Sandhu ◽  
Judith A. Seidel ◽  
Neil Patel ◽  
Toni O. Sobande ◽  
...  
Keyword(s):  
T Cells ◽  
Varicella Zoster Virus ◽  
Varicella Zoster

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.

scholarly journals P173 Investigating varicella-zoster virus-specific T cells through the lenses of HIV

2019 ◽  
Author(s):  
Carolina Moreira ◽  
Catia Perciani ◽  
Thomas Murooka ◽  
Walter Jaoko ◽  
Kelly Macdonald ◽  
...  
Keyword(s):  
T Cells ◽  
Varicella Zoster Virus ◽  
Varicella Zoster

scholarly journals Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Christiane S. Eberhardt ◽  
Andreas Wieland ◽  
Tahseen H. Nasti ◽  
Alba Grifoni ◽  
Elizabeth Wilson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Young Adults ◽  
Varicella Zoster Virus ◽  
Cd4 T Cells ◽  
Plasma Cells ◽  
Cd4 T Cell ◽  
Immune Memory ◽  
Varicella Zoster ◽  
Ifn Γ

ABSTRACT Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow. IMPORTANCE Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.

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