scholarly journals Host Range and Interference Studies of Three Classes of Pig Endogenous Retrovirus

1998 ◽  
Vol 72 (12) ◽  
pp. 9986-9991 ◽  
Author(s):  
Yasuhiro Takeuchi ◽  
Clive Patience ◽  
Saema Magre ◽  
Robin A. Weiss ◽  
Papia T. Banerjee ◽  
...  
Keyword(s):  
Host Range ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Model Systems ◽  
Type C ◽  
Interference Studies ◽  
Vector Transduction

ABSTRACT Recent interest in the use of porcine organs, tissues, and cells for xenotransplantation to humans has highlighted the need to characterize the properties of pig endogenous retroviruses (PERVs). Analysis of a variety of pig cells allowed us to isolate and identify three classes of infectious type C endogenous retrovirus (PERV-A, PERV-B, and PERV-C) which have distinct env genes but have highly homologous sequences in the rest of the genome. To study the properties of these env genes, expression plasmids for the three env genes were constructed and used to generate retrovirus vectors bearing corresponding Env proteins. Host range analyses by the vector transduction assay showed that PERV-A and PERV-B Envs have wider host ranges, including several human cell lines, compared with PERV-C Env, which infected only two pig cell lines and one human cell line. All PERVs could infect pig cells, indicating that the PERVs have a potential to replicate in pig transplants in immunosuppressed patients. Receptors for PERV-A and PERV-B were present on cells of some other species, including mink, rat, mouse, and dog, suggesting that such species may provide useful model systems to study infection and pathogenicity of PERV. In contrast, no vector transduction was observed on nonhuman primate cell lines, casting doubt on the utility of nonhuman primates as models for PERV zoonosis. Interference studies showed that the three PERV strains use receptors distinct from each other and from a number of other type C mammalian retroviruses.

scholarly journals Extended Analysis of the In Vitro Tropism of Porcine Endogenous Retrovirus

2000 ◽  
Vol 74 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Carolyn A. Wilson ◽  
Susan Wong ◽  
Matthew VanBrocklin ◽  
Mark J. Federspiel
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Line ◽  
Endogenous Retrovirus ◽  
Human Cells ◽  
Productive Infection ◽  
Porcine Endogenous Retrovirus ◽  
Productive Replication

ABSTRACT We previously reported that mitogenic activation of porcine peripheral blood mononuclear cells resulted in production of porcine endogenous retrovirus(es) (PERV[s]) capable of productively infecting human cells (C. Wilson et al., J. Virol. 72:3082–3087, 1998). We now extend that analysis to show that additional passage of isolated virus, named here PERV-NIH, through a human cell line yielded a viral population with a higher titer of infectious virus on human cells than the initial isolate. We show that in a single additional passage on a human cell line, the increase in infectivity for human cells is accounted for by selection against variants carrying pig-tropic envelope sequences (PERV-C) as well as by enrichment for replication-competent genomes. Sequence analysis of the envelope cDNA present in virions demonstrated that the envelope sequence of PERV-NIH is related to but distinct from previously reported PERV envelopes. The in vitro host range of PERV was studied in human primary cells and cell lines, as well as in cell lines from nonhuman primate and other species. This analysis reveals three patterns of susceptibility to infection among these host cells: (i) cells are resistant to infection in our assay; (ii) cells are infected by virus, as viral RNA is detected in the supernatant by reverse transcription-PCR, but the cells are not permissive to productive replication and spread; and (iii) cells are permissive to low-level productive replication. Certain cell lines were permissive for efficient productive infection and spread. These results may prove useful in designing appropriate animal models to assess the in vivo infectivity properties of PERV.

scholarly journals Infection of Nonhuman Primate Cells by Pig Endogenous Retrovirus

2000 ◽  
Vol 74 (16) ◽  
pp. 7687-7690 ◽  
Author(s):  
Juergen H. Blusch ◽  
Clive Patience ◽  
Yasuhiro Takeuchi ◽  
Christian Templin ◽  
Christian Roos ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Cell Lines ◽  
Nonhuman Primate ◽  
Endogenous Retrovirus ◽  
Papio Hamadryas ◽  
Endogenous Retroviruses ◽  
Human Donor ◽  
Baboon Model ◽  
Primate Cell ◽  
Perv Transmission

ABSTRACT The ongoing shortage of human donor organs for transplantation has catalyzed new interest in the application of pig organs (xenotransplantation). One of the biggest concerns about the transplantation of porcine grafts into humans is the transmission of pig endogenous retroviruses (PERV) to the recipients or even to other members of the community. Although nonhuman primate models are excellently suited to mimic clinical xenotransplantation settings, their value for risk assessment of PERV transmission at xenotransplantation is questionable since all of the primate cell lines tested so far have been found to be nonpermissive for PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas primary skin fibroblasts and also baboon B-cell lines are permissive for PERV infection. This suggests that a reevaluation of the suitability of the baboon model for risk assessment in xenotransplantation is critical at this point.

scholarly journals Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia

2019 ◽  
Author(s):  
Özgen Deniz ◽  
Mamataz Ahmed ◽  
Christopher D. Todd ◽  
Ana Rio-Machin ◽  
Mark A. Dawson ◽  
...  
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Endogenous Retrovirus ◽  
Epigenetic Silencing ◽  
Endogenous Retroviruses ◽  
Transcriptional Networks ◽  
Hematopoietic Malignancy ◽  
Additional Layer ◽  
Leukemia Cell Lines ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a highly aggressive hematopoietic malignancy, defined by a series of genetic and epigenetic alterations, which result in deregulation of transcriptional networks. One understudied but important source of transcriptional regulators are transposable elements (TEs), which are widespread throughout the human genome. Aberrant usage of these sequences could therefore contribute to oncogenic transcriptional circuits. However, the regulatory influence of TEs and their links to disease pathogenesis remain unexplored in AML. Using epigenomic data from AML primary samples and leukemia cell lines, we identified six endogenous retrovirus (ERV) families with AML-associated enhancer chromatin signatures that are enriched in binding of key regulators of hematopoiesis and AML pathogenesis. Using both CRISPR-mediated locus-specific genetic editing and simultaneous epigenetic silencing of multiple ERVs, we demonstrate that ERV deregulation directly alters the expression of adjacent genes in AML. Strikingly, deletion or epigenetic silencing of an ERV-derived enhancer suppressed cell growth by inducing apoptosis in leukemia cell lines. Our work reveals that ERVs are a previously unappreciated source of AML enhancers that have the potential to play key roles in leukemogenesis. We suggest that ERV activation provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive tumour heterogeneity and evolution.

scholarly journals HOST RANGE AND INTERFERENCE STUDIES OF THREE CLASSES OF PIG ENDOGENOUS RETROVIRUS

1999 ◽  
Vol 20 (4) ◽  
pp. A8 ◽  
Author(s):  
Yasuhiro Takeuchi ◽  
Clive Patience ◽  
Saema Magre ◽  
Robin Weiss ◽  
Papia Banerjee ◽  
...  
Keyword(s):  
Host Range ◽  
Endogenous Retrovirus ◽  
Interference Studies

scholarly journals Human endogenous retrovirus-W envelope (syncytin) is expressed in both villous and extravillous trophoblast populations

2006 ◽  
Vol 87 (7) ◽  
pp. 2067-2071 ◽  
Author(s):  
A. Muir ◽  
A. M. L. Lever ◽  
A. Moffett
Keyword(s):  
Cell Lines ◽  
First Trimester ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Extravillous Trophoblast ◽  
Human Endogenous Retrovirus ◽  
Human Trophoblast ◽  
Human Endogenous Retroviruses ◽  
Normal Tissues ◽  
Villous Trophoblast

The placenta is unique amongst normal tissues in transcribing numerous different human endogenous retroviruses at high levels. In this study, RT-PCR and immunohistochemistry were used to investigate the expression of syncytin in human trophoblast. Syncytin transcripts were found in first-trimester trophoblast cells with both villous and extravillous phenotypes and also in the JAR and JEG-3 choriocarcinoma cell lines. Syncytin protein was detected in villous trophoblast and in all extravillous trophoblast subpopulations of first- and second-trimester placental tissues. It was also present in ectopic trophoblast from tubal implantations. This study confirms that syncytin is expressed widely by a variety of normal human trophoblast populations, as well as choriocarcinoma cell lines.

scholarly journals Human endogenous retrovirus transcription profiles of the kidney and kidney-derived cell lines

2011 ◽  
Vol 92 (10) ◽  
pp. 2356-2366 ◽  
Author(s):  
Sonja Haupt ◽  
Michele Tisdale ◽  
Michelle Vincendeau ◽  
Mary Anne Clements ◽  
David T. Gauthier ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Line ◽  
Cell Lines ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Tissue Samples ◽  
Transcription Pattern

The human genome comprises approximately 8–9 % of human endogenous retroviruses (HERVs) that are transcribed with tissue specificity. However, relatively few organs have been examined in detail for individual differences in HERV transcription pattern, nor have tissue-to-cell culture comparisons been frequently performed. Using an HERV-specific DNA microarray, a core HERV transcription profile was established for the human kidney comparing 10 tissue samples. This core represents HERV groups expressed uniformly or nearly so in non-tumour kidney tissue. The profiles obtained from non-tumour tissues were compared to 10 renal tumour tissues (renal cell carcinoma, RCC) derived from the same individuals and additionally, to 22 RCC cell lines. No RCC cell line or tumour-specific differences were observed, suggesting that HERV transcription is not altered in RCC. However, when comparing tissue transcription to cell line transcription, there were consistent differences. The differences were irrespective of cancer state and included cell lines derived from non-tumour kidney tissue, suggesting that a specific alteration of HERV transcription occurs when establishing cell lines. In contrast to previous publications, all known HERV-derived tumour antigens, including those identified in RCC, were expressed both in multiple RCC cell lines and several non-tumour tissue-derived cell lines, a result that contrasts with findings from patient samples. The results establish the core kidney transcription pattern of HERVs and reveal differences between cell culture lines and tissue samples.

scholarly journals Epigenetic Modifier Mutations in the LL-100 Panel

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5271-5271
Author(s):  
Hilmar Quentmeier ◽  
Claudia Pommerenke ◽  
Hans G. Drexler
Keyword(s):  
Amino Acid ◽  
Drug Development ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cell ◽  
Conflicts Of Interest ◽  
Human Cancer ◽  
Human Cell Line ◽  
Dominant Negative ◽  
Epigenetic Modifier

Abstract The NCI-60 human cell line panel, developed for use in drug development comprises sixty human cancer cell lines derived from nine different tissues. Only six cell lines of the NCI-60 were derived from blood cancers. Therefore, most forms and subtypes of leukemia and lymphoma are not represented in the NCI-60 panel. To respond to this apparent gap, we suggest the novel LL-100 panel, 100 leukemia and lymphoma cell lines representing the major leukemia/lymphoma entities, for basic research and drug development. Whole exome sequencing and RNA sequencing were performed to identify mutations in 100 cell lines. Here we list the 100 cell lines, ordered by subtype and show mutations in epigenetic modifier genes. We found cell lines with mutations in ASXL1, EZH2, IDH1, TET2 and in DNMT3A. Hitherto, cell line OCI-AML3 was the only human cell line described with a DNMT3A mutation. Twenty-two percent of patients with acute myeloid leukemia contain DNMT3A mutations and the median overall survival with DNMT3A mutations is shorter than without. Most DNMT3A mutations are heterozygous and alter amino acid R882, R882H being the most common DNMT3A mutation in AML. Exogenously mutant murine R878H (equivalent to human R882H) inhibits DNMT3A activity in a dominant negative manner. We describe here that the AML cell line SET-2 carries a heterozygous G to A transition at chr2_25234373 (hg38) which leads to the DNMT3A R882H amino acid substitution. Chip-based methylation analysis revealed that the described DNMT3A targets IRF8, KLF2, HOXA11 and HOXB2 are hypomethylated in cell lines OCI-AML3 (DNMT3A R882C) and in SET-2 (DNMT3A R882H). These data suggest that SET-2 is a novel model cell line for functional analysis of the DNMT3A R882 mutation and a first gain in knowledge through data mining the LL-100 panel. Disclosures No relevant conflicts of interest to declare.

scholarly journals Overexpression of Endogenous Retroviruses and Malignancy Markers in Neuroblastoma Cell Lines by Medium-Induced Microenvironmental Changes

2021 ◽  
Vol 11 ◽  
Author(s):  
Lisa Wieland ◽  
Kristina Engel ◽  
Ines Volkmer ◽  
Anna Krüger ◽  
Guido Posern ◽  
...  
Keyword(s):  
Stem Cell ◽  
Quantitative Pcr ◽  
Cell Lines ◽  
Transcriptional Activation ◽  
Neuroblastoma Cell ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Tumor Escape ◽  
Stem Cell Medium ◽  
Cell Medium

Neuroblastoma (NB) is the commonest solid tumor outside the central nervous system in infancy and childhood with a unique biological heterogeneity. In patients with advanced, metastasizing neuroblastoma, treatment failure and poor prognosis is often marked by resistance to chemo- or immunotherapy. Thus, identification of robust biomarkers seems essential for understanding tumor progression and developing effective therapy. Here, we have studied the expression of human endogenous retroviruses (HERV) as potential targets in NB cell lines during stem-cell medium-induced microenvironmental change. Quantitative PCR revealed that relative expression of the HERV-K family and HERV-W1 ENV were increased in all three NB cell lines after incubation in stem-cell medium. Virus transcriptome analyses revealed the transcriptional activation of three endogenous retrovirus elements: HERV-R ENV (ERV3-1), HERV-E1 and HERV-Fc2 ENV (ERVFC1-1). Known malignancy markers in NB, e.g. proto-oncogenic MYC or MYCN were expressed highly heterogeneously in the three investigated NB cell lines with up-regulation of MYC and MYCN upon medium-induced microenvironmental change. In addition, SiMa cells exclusively showed a phenotype switching from loosely-adherent monolayers to low proliferating grape-like cellular aggregates, which was accompanied by an enhanced CD133 expression. Interestingly, the overexpression of HERV was associated with a significant elevation of immune checkpoint molecule CD200 in both quantitative PCR and RNA-seq analysis suggesting tumor escape mechanism in NB cell lines after incubation in serum-free stem cell medium.

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