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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88932 |
| Date | 10 January 2024 |
| Creators | Gröger, Victoria, Wieland, Lisa, Naumann, Marcel, Meinecke, Ann-Christin, Meinhardt, Beate, Rossner, Steffen, Ihling, Christian, Emmer, Alexander, Staege, Martin S., Cynis, Holger |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7855, 10.3390/ijms21217855 |
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