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Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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1996 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 67, no 3, 451-456 p.Article in journal (Refereed) Published
Abstract [en]

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb is widely expressed in human tissues and cells, but gag-pol mRNA has not been found. Further, the env gp70 gene contains an open reading frame throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so far is in placenta and the lowest in cytotrophoblasts and choriocarcinoma cell lines. In this report we have studied ERV3 mRNA and protein expression in the human monoblastic cell line U-937 during differentiation into monocytes/macrophages. Differentiation of U-937 cells was induced by 1,25a-dihydroxyvitamin D3 (vitD3), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The expression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic development. Using TPA, the expression of ERV3 env was detected as 9- and 3.5-kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Induction with vitD3, IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represents an excellent model system for further studies to study the relationship between ERV3 expression and cellular differentiation.

Place, publisher, year, edition, pages
1996. Vol. 67, no 3, 451-456 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89898DOI: 10.1002/(SICI)1097-0215(19960729)67:3<451::AID-IJC23>3.0.CO;2-9PubMedID: 8707424OAI: oai:DiVA.org:uu-89898DiVA: diva2:161741
Available from: 2002-05-10 Created: 2002-05-10 Last updated: 2010-08-13Bibliographically approved
In thesis
1. Studies on Human Endogenous Retroviruses (HERVs) with Special Focus on ERV3
Open this publication in new window or tab >>Studies on Human Endogenous Retroviruses (HERVs) with Special Focus on ERV3
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Human endogenous retroviruses (HERVs) represent approximately 7% of the human genome. This investigation was focused on one particular HERV, ERV3, with the main purpose of characterising its gene expression patterns and genomic distribution of ERV3-like sequences. Furthermore, this careful expression study should provide insights into the biological role of HERVs. The impact of HERVs in health and disease is not yet clarified. ERV3 is expressed as three envelope (env) transcripts, of which two also contain a cellular gene, H-plk (human proviral linked Krüppel). ERV3 env expression was mainly investigated at the RNA level. The gene expression of two other HERVs, HERV-K and HERV-E was analysed and compared with ERV3 activity.

Real-time PCRs were developed and in combination with in situ hybridisation, it was found that ERV3 is expressed in a tissue- and cell-specific way. High levels of ERV3 mRNA (up to six times over Histone3.3) were demonstrated in placenta, sebaceous glands, foetal and adult adrenal glands, brown adipose tissue, corpus luteum, pituitary gland, thymus and testis. In monocytic cells including both normal monocytes and malignant U-937 cells, elevated mRNA levels were observed after retinoic acid (RA)-induced differentiation. ERV3-encoded Env protein was detected in selected cases, one following RA-treatment. In addition, several new ERV3-like sequences were discovered in the human genome.

ERV3 was found to have conserved open reading frames in contrast to other ERV3-like sequences in the human genome. This suggests that ERV3 may be involved in important cellular processes such as differentiation, cell fusion, immunomodulation and protection against infectious retroviruses. The developed techniques and obtained results will allow further studies of HERV expression to better correlate HERV activity to both normal development and disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 61 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1165
Genetics, human endogenous retroviruses, HERV, ERV3, expression, in situ hybridisation, real-time PCR, U-937, retinoic acid., Genetik
National Category
Medical Genetics
Research subject
urn:nbn:se:uu:diva-2097 (URN)91-554-5342-2 (ISBN)
Public defence
2002-06-01, Rudbecksalen, Uppsala, 09:15
Available from: 2002-05-10 Created: 2002-05-10Bibliographically approved

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