ArticleCell genomics2025
Indels allow antiviral proteins to evolve functional novelty inaccessible by missense mutations.
Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- Cross-species gene redesign leveraging ortholog information and generative modeling.Nature communications · 2026Article
- Deep models of protein evolution in time generate realistic evolutionary trajectories and functional proteins.bioRxiv : the preprint server for biology · 2026Article
- Deep indel mutagenesis reveals the impact of amino acid insertions and deletions on protein stability and function.Nature communications · 2025Article
- Structural and energetic analysis of stabilizing indel mutations.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive deletion scan of anti-CRISPR AcrIIA4 reveals essential and dispensable domains for Cas9 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comprehensive deletion scan of anti-CRISPR AcrIIA4 reveals essential and dispensable domains for Cas9 inhibition.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
- Update of
Authors and funding
7 authors.
Funding
Abstract
Antiviral proteins often evolve rapidly at virus-binding interfaces to defend against new viruses. We investigated whether antiviral adaptation via missense mutations might face limits, which insertion or deletion mutations (indels) could overcome. Using high-throughput saturation missense mutagenesis, we identify one such case of a nearly insurmountable evolutionary challenge: the human anti-retroviral protein TRIM5α requires more than five missense mutations in its specificity-determining v1 loop to restrict a divergent simian immunodeficiency virus (SIV). However, through a novel saturating indel scanning methodology, we find that duplicating just one amino acid in v1 enables human TRIM5α to potently restrict SIV in a single evolutionary step. Moreover, natural primate TRIM5α v1 loops have evolved indels that confer novel antiviral specificities. Thus, indels enable antiviral proteins to overcome viral challenges otherwise inaccessible by missense mutations. Our findings reveal the potential of often-overlooked indel mutations in driving protein innovation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.