Formation of HERV-K and HERV-Fc1 envelope family members is suppressed on transcriptional and translational level
| Autor: | Martin S. Staege, Holger Cynis, Lisa Wieland, Ann-Christin Meinecke, Alexander Emmer, Beate Meinhardt, Victoria Gröger, Steffen Rossner, Marcel Naumann, Christian Ihling |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Glycosylation Transcription Genetic viruses Molecular Conformation translation human endogenous retroviruses lcsh:Chemistry 0302 clinical medicine Viral Envelope Proteins Transcription (biology) Chlorocebus aethiops Protein maturation lcsh:QH301-705.5 Endoplasmic Reticulum Chaperone BiP Spectroscopy Superantigens codon usage General Medicine Computer Science Applications Cell biology 030220 oncology & carcinogenesis Codon usage bias COS Cells transcription Biology Catalysis Article Cell Line Inorganic Chemistry 03 medical and health sciences Open Reading Frames Viral envelope expression Animals Humans RNA Messenger Physical and Theoretical Chemistry Molecular Biology Gene Cell-Free System Organic Chemistry Endogenous Retroviruses Membrane Proteins Open reading frame 030104 developmental biology HEK293 Cells lcsh:Biology (General) lcsh:QD1-999 Gene Expression Regulation A549 Cells Protein Biosynthesis Unfolded protein response Nucleic Acid Conformation Human genome |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 21 International Journal of Molecular Sciences, Vol 21, Iss 7855, p 7855 (2020) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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