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Peer-reviewedCC BYThe EMBO Journal

Alternative splicing broadens antiviral diversity at the human OAS2 locus

  • Emma L. Davies1
  • Alegna Calderon Nuñez2
  • Allison L Ward2
  • Hanna Sowar2
  • Eilidh Rivers2
  • Arda Balci2
  • Daniel Mair2
  • Elliot Moorhouse2
  • Jake Towers2
  • Arthur Wickenhagen2
  • Matthew L. Turnbull2
  • Massimo Palmarini2
2 more authors
  • Sam J. Wilson3
  • Adam J. Fletcher4
4 affiliations
  1. 1MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK. [email protected]
  2. 2MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
  3. 3Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, Cambridge, UK. [email protected]
  4. 4MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK. [email protected]
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Abstract

Interferons (IFN) are cytokines that regulate the expression of hundreds of genes during viral infections to generate a broadly antiviral environment in the stimulated cell. Antiviral breadth is provided by the concurrent expression of many individual IFN-stimulated genes (ISG), each encoding a protein with often exquisite antiviral specificity. Here, we identify mechanistic plasticity at a single genetic locus as a novel mechanism to diversify the antiviral profile of human cells. Through alternative splicing, the OAS2 gene encodes two antiviral molecules with distinct target specificities. The shorter OAS2 p69 isoform restricts seasonal human coronavirus OC43 (HCoV-OC43), whereas the longer p71 isoform restricts picornavirus Cardiovirus A (EMCV). The restriction profile is determined by the variable length OAS2 C-terminal tails. Notably, these antiviral activities differ in their dependence on RNase L, suggesting that alternative splicing separates canonical restriction and virus sensing functions across two distinct OAS2 polypeptides. Together, these findings show how alternative splicing expands antiviral diversity at the human OAS2 locus.

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Cite

BibTeXRIS
BibTeX
@article{davies2026alternative,
  title = {{Alternative splicing broadens antiviral diversity at the human OAS2 locus}},
  author = {Emma L. Davies and Alegna Calderon Nuñez and Allison L Ward and Hanna Sowar and Eilidh Rivers and Arda Balci and Daniel Mair and Elliot Moorhouse and Jake Towers and Arthur Wickenhagen and Matthew L. Turnbull and Massimo Palmarini and Sam J. Wilson and Adam J. Fletcher},
  journal = {The EMBO Journal},
  year = {2026},
  month = jun,
  doi = {10.1038/s44318-026-00825-w},
  url = {https://doi.org/10.1038/s44318-026-00825-w},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Alternative splicing broadens antiviral diversity at the human OAS2 locus
AU  - Emma L. Davies
AU  - Alegna Calderon Nuñez
AU  - Allison L Ward
AU  - Hanna Sowar
AU  - Eilidh Rivers
AU  - Arda Balci
AU  - Daniel Mair
AU  - Elliot Moorhouse
AU  - Jake Towers
AU  - Arthur Wickenhagen
AU  - Matthew L. Turnbull
AU  - Massimo Palmarini
AU  - Sam J. Wilson
AU  - Adam J. Fletcher
PY  - 2026
DA  - 2026/06/03
JO  - The EMBO Journal
DO  - 10.1038/s44318-026-00825-w
UR  - https://doi.org/10.1038/s44318-026-00825-w
AB  - Interferons (IFN) are cytokines that regulate the expression of hundreds of genes during viral infections to generate a broadly antiviral environment in the stimulated cell. Antiviral breadth is provided by the concurrent expression of many individual IFN-stimulated genes (ISG), each encoding a protein with often exquisite antiviral specificity. Here, we identify mechanistic plasticity at a single genetic locus as a novel mechanism to diversify the antiviral profile of human cells. Through alternative splicing, the OAS2 gene encodes two antiviral molecules with distinct target specificities. The shorter OAS2 p69 isoform restricts seasonal human coronavirus OC43 (HCoV-OC43), whereas the longer p71 isoform restricts picornavirus Cardiovirus A (EMCV). The restriction profile is determined by the variable length OAS2 C-terminal tails. Notably, these antiviral activities differ in their dependence on RNase L, suggesting that alternative splicing separates canonical restriction and virus sensing functions across two distinct OAS2 polypeptides. Together, these findings show how alternative splicing expands antiviral diversity at the human OAS2 locus.
SN  - 0261-4189
SN  - 1460-2075
ER  -