Article Dans Une Revue RNA Année : 2025

The codon context provides cis-acting immune evasion for the human papilloma virus (HPV) E6

Résumé

Human papilloma viruses (HPV) are linked to cancers but how virus-carrying tumor cells express HPV-encoded antigens without attracting the immune system is still poorly understood. Here we show how low- and high-risk HPV types equally exploit a cis-acting mechanism to limit the translation of the E6 mRNA, reducing the production of antigenic peptide substrates for the major histocompatibility class I (MHC-I) pathway. Introducing particular combinations of preferable codons throughout the HPV-16 E6 mRNA promotes mRNA translation and production of antigenic peptide substrates in mammalian cells but has minimal impact on E6 synthesis in S. cerevisiae. Using a gradual synonymous codon exchange, we identified a codon series with a significant effect on E6 translation rate. Unexpectedly, changing four non-preferable codons to preferable codons in the wild-type sequence resulted in an approximate 50% reduction in E6 expression. However, five additional changes to preferable codon further upstream shifted this inhibition to a strong induction of E6 expression, while they had no effect when introduced alone. These findings suggest a nuanced relationship between tRNA pools and translation rate, emphasizing how HPV uses codon usage to evade immune detection.

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Dates et versions

hal-05311429 , version 1 (13-10-2025)

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Aikaterini Thermou, Chrysoula Daskalogianni, Lixiao Wang, Laurence Malbert-Colas, Van-Trang Dinh, et al.. The codon context provides cis-acting immune evasion for the human papilloma virus (HPV) E6. RNA, 2025, pp.rna.080390.125. ⟨10.1261/rna.080390.125⟩. ⟨hal-05311429⟩
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