Evidence map›Paper›PMID 40700459›Full record

ArticlePLoS pathogens2025

A functional interleukin-4 homolog is encoded in the genome of infectious laryngotracheitis virus: Unveiling a novel virulence factor.

Jeremy D Volkening, Stephen J Spatz, Maricarmen Garcia, Teresa A Ross, Daniel A Maekawa, Kenneth S Rosenthal, Ana C Zamora, April Skipper, Julia R Blakey, Rashan Paudel

Erratum issuedAbstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Jeremy D VolkeningBASE2BIO, Oshkosh, Wisconsin, United States of America.ORCID 0000-0002-8892-7155
Stephen J SpatzUS National Poultry Research Center, ARS-USDA, Athens, Georgia, United States of America.ORCID 0000-0002-1545-5855
Maricarmen GarciaUniversity of Georgia, College of Veterinary Medicine, Department of Population Health, Poultry Diagnostic Research Center, Athens, Georgia, United States of America.
Teresa A RossUS National Poultry Research Center, ARS-USDA, Athens, Georgia, United States of America.
Daniel A MaekawaMerck Animal Health, De Soto, Kansas, United States of America.
Kenneth S RosenthalDepartment of Biomedical Sciences, Augusta University/University of Georgia Medical Partnership, Athens, Georgia, United States of America.
Ana C ZamoraUniversity of Georgia, College of Veterinary Medicine, Department of Population Health, Poultry Diagnostic Research Center, Athens, Georgia, United States of America.
April SkipperUniversity of Georgia, College of Veterinary Medicine, Department of Population Health, Poultry Diagnostic Research Center, Athens, Georgia, United States of America.
Julia R BlakeyUS National Poultry Research Center, ARS-USDA, Athens, Georgia, United States of America.
Rashan PaudelUniversity of Georgia, College of Veterinary Medicine, Department of Population Health, Poultry Diagnostic Research Center, Athens, Georgia, United States of America.

Funding

Agricultural Research Service (ARS) 6040-32000-083-000D
6 · The paper itself

Abstract

Herpesviruses have evolved numerous immune evasion tactics, persisting within their hosts through self-perpetuating strategies. One such tactic involves acquiring functional copies of host genes encoding cytokines such as IL-6 (HHV-8), IL-10 (HHV-4, HHV-5), and IL-17 (SaHV-2). These viral mimics, or virokines, can bind to cellular receptors, modulating the natural cytokine signaling to manipulate the immune response in favor of the virus or stimulate target cell growth to enhance virus replication. In the course of full-length cDNA sequencing of infectious laryngotracheitis virus (ILTV) transcripts, a previously unknown highly spliced gene was discovered in the viral genome predicted to encode a 147 amino acid protein with similarity to vertebrate interleukin-4. The three-intron gene structure was precisely conserved with chicken and other vertebrate IL-4 homologs, and the amino acid sequence displayed structural conservation with vertebrate homologs at the primary, secondary, and tertiary levels based on computational modeling. The viral IL-4 gene was subsequently identified in all sequenced ILTV genomes. The mature transcript was highly expressed both in vitro and in vivo, and protein expression in infected cells was confirmed using LC-MS/MS. Phylogenetic analyses, along with the conserved gene structure, suggested direct capture from a Galliformes host. Functionally, an LPS-stimulation assay showed that the expressed viral IL-4 homolog stimulated nitric oxide production in a macrophage cell line at comparable levels to recombinant chicken IL-4. A recombinant virus lacking vIL-4 exhibited slightly higher titers in cell culture compared to the parental strain. In vivo bird studies demonstrated reduced pathogenicity of the vIL-4 knockout compared to wildtype. These results represent the first report of a previously unknown virokine encoded in the ILTV genome expressing a functional IL-4 homolog and virulence factor.

Indexed as

Genome, ViralHerpesviridae InfectionsHerpesvirus 1, GallidInterleukin-4Viral ProteinsVirulence FactorsAmino Acid SequenceAnimalsChickensMiceVirus ReplicationInterleukin-4Viral ProteinsVirulence Factors

Identifiers

PMID40700459
PMCPMC12327624

What Socratic holds

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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 Socratic graph.