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Front. Microbiol. | doi: 10.3389/fmicb.2018.00287

Investigation of endogenous retrovirus-associated genes in a neuroblastoma model after treatment with hypoxia-mimetic cobalt chloride

 Christine Brütting1*, Harini Narasimhan1, Frank Hoffmann1, Malte E. Kornhuber1,  Martin S. Staege1 and  Alexander Emmer1
  • 1Martin Luther University of Halle-Wittenberg, Germany


Human endogenous retroviruses have been found to be associated with different diseases, e.g. multiple sclerosis. Most human endogenous retroviruses integrated in our genome are not competent to replicate and these sequences are presumably silent. However, transcription of human endogenous retroviruses can be reactivated e.g. by hypoxia. Interestingly, multiple sclerosis has been linked to hypoxia since decades. As some patterns of demyelination are similar to white matter ischemia, hypoxic damage is discussed. Therefore, we are interested in the association between hypoxia and endogenous retroviruses. As a model, we used human SH-SY5Y neuroblastoma cells after treatment with the hypoxia-mimetic cobalt chloride and analyzed differences in the gene expression profiles in comparison to untreated cells. The vicinity of up-regulated genes was scanned for endogenous retrovirus-derived sequences. Five genes were found to be strongly up-regulated in SH-SY5Y cells after treatment with cobalt chloride: clusterin, glutathione peroxidase 3, insulin-like growth factor 2, solute carrier family 7 member 11, and neural precursor cell expressed developmentally down-regulated protein 9. In the vicinity of these genes we identified large (> 1,000 bp) open reading frames. All of these open reading frames showed similarities to proteins from retro-transcribing viruses. We found the highest homology (93 %) between retrovirus envelope sequences and a sequence in the vicinity of neural precursor cell expressed developmentally down-regulated protein 9. This sequence encodes the human ERV group FRD member 1, the encoded protein product is called syncytin 2. Transfection of syncytin 2 into the well characterized Ewing sarcoma cell line A673 was not able to modulate the low immunostimulatory activity of this cell line. Future research is needed to determine whether the identified genes and the human endogenous retrovirus group FRD member 1 might play a role in the etiology of multiple sclerosis.

Keywords: Endogenous Retroviruses, Open Reading Frames, Neuroblastoma, Multiple Sclerosis, neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), Hypoxia, Brain, human endogenous retrovirus group FRD member 1 (ERVFRD-1), HERV-FRD

Received: 29 Sep 2017; Accepted: 07 Feb 2018.

Edited by:

Gkikas Magiorkinis, National and Kapodistrian University of Athens, Greece

Reviewed by:

Masaaki Miyazawa, Kindai University, Japan
Tara P. Hurst, Abcam (United Kingdom), United Kingdom  

Copyright: © 2018 Brütting, Narasimhan, Hoffmann, Kornhuber, Staege and Emmer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Christine Brütting, Martin Luther University of Halle-Wittenberg, Halle, Germany,