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Coronaviruses remodel the mature human tRNAome to modulate infection

Yining Wang1, Xin Wang1, Amine Avan1

  • 1Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Virulence
|October 28, 2025
PubMed

Insights

Human coronaviruses remodel the host tRNAome for infection, with varying sensitivities between species. Manipulating amino acids or transfer RNAs (tRNAs) impacts viral replication, offering new therapeutic targets.

Area of Science:

  • Virology
  • Molecular Biology
  • Host-Pathogen Interactions

Background:

  • Virus-host interactions are incompletely understood, particularly the translational decoding phase.
  • Transfer RNAs (tRNAs) play a critical role in translating genetic information into proteins.
  • Human coronaviruses exhibit distinct codon usage compared to their host.

Purpose of the Study:

  • To investigate the role of the host tRNAome in human coronavirus infection.
  • To identify specific tRNAs and amino acids involved in coronavirus replication.
  • To explore potential therapeutic strategies targeting translational decoding.

Main Methods:

  • Codon usage analysis of human coronaviruses and host cells.
  • Quantification of the human tRNAome during infection.
  • Experimental manipulation of amino acid availability and tRNA modification enzymes (TRNT1, Aspartyl-tRNA Synthetase 1).

Main Results:

  • Human coronaviruses upregulate the host tRNAome during infection.
  • Depriving amino acids or inhibiting tRNA modification enzymes (TRNT1) reduced viral infection.
  • tRNA-Asn-AUU was identified as crucial for decoding various human coronaviruses.
  • Asparagine (Asn) deprivation significantly inhibited CoV-229E but had less effect on NL63 and SARS-CoV-2.

Conclusions:

  • Human coronaviruses manipulate the host mature tRNAome to enhance viral replication.
  • Interference at the single amino acid or tRNA level affects different coronavirus species uniquely.
  • These findings offer novel insights into virus-host interactions and potential antiviral targets.
Keywords:
Coronavirusesamino acidinfectiontRNA

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