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From Recoding to Peptides for MHC Class I Immune Display: Enriching Viral Expression, Virus Vulnerability and Virus Evasion

Journal

VIRUSES-BASEL
Volume 13, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/v13071251

Keywords

StopGo; ribosomal frameshifting; stop codon readthrough; codon redefinition; selenocysteine; bet hedging; DRiPs; ribosome structure; cancer

Categories

Funding

  1. Irish Research Council Advanced Laureate Award [IRCLA/2019/74]
  2. Carbery group

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Many viruses use recoding strategies to increase coding capacity and generate protein products with different functions; sacrificing accuracy for speed in viral expression can create opportunities for host immune defense; some viruses utilize recoding to evade immune responses or specific drugs.
Many viruses, especially RNA viruses, utilize programmed ribosomal frameshifting and/or stop codon readthrough in their expression, and in the decoding of a few a UGA is dynamically redefined to specify selenocysteine. This recoding can effectively increase viral coding capacity and generate a set ratio of products with the same N-terminal domain(s) but different C-terminal domains. Recoding can also be regulatory or generate a product with the non-universal 21st directly encoded amino acid. Selection for translation speed in the expression of many viruses at the expense of fidelity creates host immune defensive opportunities. In contrast to host opportunism, certain viruses, including some persistent viruses, utilize recoding or adventitious frameshifting as part of their strategy to evade an immune response or specific drugs. Several instances of recoding in small intensively studied viruses escaped detection for many years and their identification resolved dilemmas. The fundamental importance of ribosome ratcheting is consistent with the initial strong view of invariant triplet decoding which however did not foresee the possibility of transitory anticodon:codon dissociation. Deep level dynamics and structural understanding of recoding is underway, and a high level structure relevant to the frameshifting required for expression of the SARS CoV-2 genome has just been determined.

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