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Open AccessArticle

Formation of HERV-K and HERV-Fc1 Envelope Family Members is Suppressed on Transcriptional and Translational Level

1
Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, Weinbergweg 22, 06120 Halle, Germany
2
Department of Neurology, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle, Germany
3
Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle, Germany
4
Paul Flechsig Institute for Brain Research, Leipzig University, Liebigstraße 19, 04103 Leipzig, Germany
5
Department of Pharmaceutical Chemistry & Bioanalytics, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, Kurt-Mothes-Str. 3a, 06120 Halle, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Int. J. Mol. Sci. 2020, 21(21), 7855; https://doi.org/10.3390/ijms21217855
Received: 4 September 2020 / Revised: 15 October 2020 / Accepted: 21 October 2020 / Published: 23 October 2020
(This article belongs to the Special Issue Endogenous Retroviruses: Functions at Molecular Level)
The human genome comprises 8% sequences of retroviral origin, so-called human endogenous retroviruses (HERVs). Most of these proviral sequences are defective, but some possess open reading frames. They can lead to the formation of viral transcripts, when activated by intrinsic and extrinsic factors. HERVs are thought to play a pathological role in inflammatory diseases and cancer. Since the consequences of activated proviral sequences in the human body are largely unexplored, selected envelope proteins of human endogenous retroviruses associated with inflammatory diseases, namely HERV-K18, HERV-K113, and HERV-Fc1, were investigated in the present study. A formation of glycosylated envelope proteins was demonstrated in different mammalian cell lines. Nevertheless, protein maturation seemed to be incomplete as no transport to the plasma membrane was observed. Instead, the proteins remained in the ER where they induced the expression of genes involved in unfolded protein response, such as HSPA5 and sXBP1. Furthermore, low expression levels of native envelope proteins were increased by codon optimization. Cell-free expression systems showed that both the transcriptional and translational level is affected. By generating different codon-optimized variants of HERV-K113 envelope, the influence of single rare t-RNA pools in certain cell lines was demonstrated. The mRNA secondary structure also appears to play an important role in the translation of the tested viral envelope proteins. In summary, the formation of certain HERV proteins is basically possible. However, their complete maturation and thus full biologic activity seems to depend on additional factors that might be disease-specific and await elucidation in the future. View Full-Text
Keywords: human endogenous retroviruses; expression; codon usage; transcription; translation human endogenous retroviruses; expression; codon usage; transcription; translation
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MDPI and ACS Style

Gröger, V.; Wieland, L.; Naumann, M.; Meinecke, A.-C.; Meinhardt, B.; Rossner, S.; Ihling, C.; Emmer, A.; Staege, M.S.; Cynis, H. Formation of HERV-K and HERV-Fc1 Envelope Family Members is Suppressed on Transcriptional and Translational Level. Int. J. Mol. Sci. 2020, 21, 7855.

AMA Style

Gröger V, Wieland L, Naumann M, Meinecke A-C, Meinhardt B, Rossner S, Ihling C, Emmer A, Staege MS, Cynis H. Formation of HERV-K and HERV-Fc1 Envelope Family Members is Suppressed on Transcriptional and Translational Level. International Journal of Molecular Sciences. 2020; 21(21):7855.

Chicago/Turabian Style

Gröger, Victoria; Wieland, Lisa; Naumann, Marcel; Meinecke, Ann-Christin; Meinhardt, Beate; Rossner, Steffen; Ihling, Christian; Emmer, Alexander; Staege, Martin S.; Cynis, Holger. 2020. "Formation of HERV-K and HERV-Fc1 Envelope Family Members is Suppressed on Transcriptional and Translational Level" Int. J. Mol. Sci. 21, no. 21: 7855.

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