Evidence map›Paper›PMID 38407436›Full record

ArticleNucleic acids research2024

Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome.

Jordan N Ranum, Mitchell P Ledwith, Fadi G Alnaji, Meghan Diefenbacher, Richard Orton, Elizabeth Sloan, Melissa Güereca, Elizabeth M Feltman, Katherine Smollett, Ana da Silva Filipe and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

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  7. Spatio-temporal modelling ofbioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 3 countries.

Jordan N RanumMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0009-0003-3351-1528
Mitchell P LedwithMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Fadi G AlnajiDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.ORCID 0000-0002-2893-9832
Meghan DiefenbacherDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.ORCID 0000-0002-8818-3686
Richard OrtonMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.ORCID 0000-0002-3389-4325
Elizabeth SloanMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
Melissa GüerecaDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Elizabeth M FeltmanMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Katherine SmollettMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.ORCID 0000-0001-7961-7377
Ana da Silva FilipeMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.ORCID 0000-0002-9442-2903
Michaela ConleyMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.ORCID 0000-0002-3457-1149
Alistair B RussellDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-5342-2309
Christopher B BrookeDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.ORCID 0000-0002-6815-1193
Edward HutchinsonMRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.ORCID 0000-0003-3673-9096
Andrew MehleMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0000-0001-6060-4330
MRC University of Glasgow Centre for Virus Research · GBUniversity of Wisconsin–Madison · USUniversity of Illinois Urbana-Champaign · USUniversity of California San Diego · USAgency for Science, Technology and Research · SG

Funding

The effects of influenza virus genomic heterogeneity on replication dynamics and the host responseR01AI139246 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BROOKE, CHRISTOPHER BYRON · 2018 to 2022
$1.9M
Understanding evasion of cell intrinsic innate immunity in viral populations with high rates of replicative failureR35GM147031 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alistair B Russell · 2022 to 2026
$1.9M
Medical Research Council MC_UU_00034/1Medical Research Council MC_UU_00034/5Medical Research Council MC_UU_12014/12Medical Research Council MC_UU_12014/9NIAID NIH HHS R01 AI139246NIGMS NIH HHS R35 GM147031
6 · The paper itself

Abstract

Productive infections by RNA viruses require faithful replication of the entire genome. Yet many RNA viruses also produce deletion-containing viral genomes (DelVGs), aberrant replication products with large internal deletions. DelVGs interfere with the replication of wild-type virus and their presence in patients is associated with better clinical outcomes. The DelVG RNA itself is hypothesized to confer this interfering activity. DelVGs antagonize replication by out-competing the full-length genome and triggering innate immune responses. Here, we identify an additionally inhibitory mechanism mediated by a new class of viral proteins encoded by DelVGs. We identified hundreds of cryptic viral proteins translated from DelVGs. These DelVG-encoded proteins (DPRs) include canonical viral proteins with large internal deletions, as well as proteins with novel C-termini translated from alternative reading frames. Many DPRs retain functional domains shared with their full-length counterparts, suggesting they may have activity during infection. Mechanistic studies of DPRs derived from the influenza virus protein PB2 showed that they poison replication of wild-type virus by acting as dominant-negative inhibitors of the viral polymerase. These findings reveal that DelVGs have a dual inhibitory mechanism, acting at both the RNA and protein level. They further show that DPRs have the potential to dramatically expand the functional proteomes of diverse RNA viruses.

Indexed as

Genome, ViralInfluenza A virusProteomeViral ProteinsAnimalsCell LineDogsHumansRNA, ViralSequence DeletionVirus ReplicationProteomeRNA, ViralViral Proteins

Identifiers

PMID38407436
PMCPMC11014358
OpenAlexW4392168905

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.