Research
Transactivation of elements in the human endogenous retrovirus W family by viral infection
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* Corresponding author: Christoffer Nellåker christoffer.nellaker@ki.se
1 The Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden
2 The Stanley Division of Developmental Neurovirology, The Johns Hopkins University School of Medicine, 600 N Wolfe Street, Blalock 1105, Baltimore, MD, 21287-4933, USA
3 UMR 2714 CNRS-bioMérieux, IFR128 BioSciences Lyon-Gerland Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon cedex 07, France
Retrovirology 2006, 3:44 doi:10.1186/1742-4690-3-44
Published: 6 July 2006Abstract
Background
Aberrant expression of human endogenous retrovirus (HERV) elements in the W family has previously been associated with schizophrenia, multiple sclerosis and preeclampsia. Little is know regarding the basal expression, transcriptional regulation and functional significance of individual HERV-elements. Since viral infections have previously been reported to transactivate retroviral long terminal repeat regions we examined the basal expression of HERV-W elements and following infections by influenza A/WSN/33 and Herpes simplex 1 viruses in human cell-lines.
Methods
Relative levels of transcripts encoding HERV-W elements and cellular genes were analyzed by qPCR methods. An analysis of amplicon melting temperatures was used to detect variations in the frequencies of amplicons in discrete ranges of such melting temperatures. These frequency-distributions were taken as proxy markers for the repertoires of transcribed HERV-W elements in the cells.
Results
We report cell-specific expression patterns of HERV-W elements during base-line conditions. Expressed elements include those with intact regulatory long terminal repeat regions (LTRs) as well as elements flanked by truncated LTRs. Subsets of HERV-W elements were transactivated by viral infection in the different cell-lines. Transcriptional activation of these elements, including that encoding syncytin, was dependent on viral replication and was not induced by antiviral responses. Serum deprivation of cells induced similar changes in the expression of HERV-W elements suggesting that the observed phenomena are, in part, an effect of cellular stress.
Conclusion
We found that HERV-W elements, including elements lacking regulatory LTRs, are expressed in cell-specific patterns which can be modulated by environmental influences. This brings into light that mechanisms behind the regulation of expression of HERV-W elements are more complex than previously assumed and suggests biological functions of these transcripts.