Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 38 min ago
Peer-reviewedCC BY-NC-NDPoultry science

Fiber-2 induces autolysosome dysfunction and impairs autophagic flux to promote FAdV-4 replication

  • Qinqin Sun1
  • Lianshun Zhang1
  • Yutong Liu1
  • Junze Chen1
  • Siting Zheng1
  • Lijin Liu1
  • Honglin Xie1
  • Qiang Fu1
  1. 1School of Animal Science and Technology, Foshan University, Foshan, China
Read full textPDFDOICite

Abstract

Fowl adenovirus serotype 4 (FAdV-4) causes hepatitis–hydropericardium syndrome in poultry, yet viral subversion of host autophagy remains unclear. Here, we investigated the role of the viral structural protein Fiber-2 in modulating the host autophagy-lysosome pathway. Transcriptomic profiling of LMH cells expressing Fiber-2 revealed coordinated upregulation of autophagy-related genes, validated by quantitative PCR. Functional assays demonstrated that Fiber-2 expression leads to autophagosome accumulation and impaired autophagic flux, as shown by LC3-II/p62 analysis, tandem fluorescent LC3 reporter imaging, Bafilomycin A1 treatment, and transmission electron microscopy. Fiber-2 predominantly localizes to late endosomes and lysosomes, and GFP-Galectin-3 reporter assays indicate that it disrupts lysosomal membrane integrity rather than blocking autophagosome-lysosome fusion. Co-immunoprecipitation (Co-IP) and enrichment analyses identified BECN1, a key autophagy regulator, as a Fiber-2-interacting protein, and associated host proteins were enriched in autophagy-related pathways. Finally, CRISPR/Cas9-mediated deletion of Fiber-2 significantly reduced FAdV-4 replication at later stages of infection, consistent with a proviral role for Fiber-2. These findings indicate that Fiber-2 disrupts autophagic flux by inducing lysosomal dysfunction and membrane damage, thereby promoting FAdV-4 replication and uncovering a previously unrecognized mechanism of viral subversion of host degradative pathways.

Related

  1. A premature ovarian insufficiency-associated LMD-3 point mutation impairs protein stability and causes autophagic-lysosomal dysfunction in Caenorhabditis elegans
    Yile Zhai, Tiantian Wang, Meixi Gong +4
    PLOS OnePeer-reviewedCC BY 4.0Full textCell biologyGenetics & genomicsPLOSPMC
  2. Hyperactivation of the AXL-ICD/SIRT2 axis by Amyloid-β impairs astrocytic autophagic flux and exacerbates neuroinflammation
    T. Y. Kim, M. Bhalla, U. P. Park +9
    bioRxivPreprintCC BY-NC-NDFull textNeurosciencebioRxiv
  3. TRIM23 prevents adenovirus replication by p62-mediated selective autophagic degradation of viral E1A protein
    Nan Sun, Jikai Zhang, Banruo Xia +11
    PLOS PathogensPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationCell biologyPLOS
  4. Acute fentanyl induces opposing directions of changes in tonic and phasic dopamine release patterns and impairs Pavlovian task performance
    Oliver P. Culver, Ren E. Thigpen, Thomas C. Jhou
    Neuropsychopharmacology : official publication of the American College of NeuropsychopharmacologyPeer-reviewedLicence not statedFull text1 citedNeurosciencePMC
  5. Hydroxychloroquine suppresses replication of PRRSV via dual regulation of autophagic flux and NF-κB-driven inflammatory signaling
    Ruirui Ye, Pengzhan Yuan, Guoxin Zheng +5
    Veterinary ResearchPeer-reviewedCC BY 4.0Full textZoology & animal behaviourPMCHAL

Cite

BibTeXRIS
BibTeX
@article{sun2026fiber2,
  title = {{Fiber-2 induces autolysosome dysfunction and impairs autophagic flux to promote FAdV-4 replication}},
  author = {Qinqin Sun and Lianshun Zhang and Yutong Liu and Junze Chen and Siting Zheng and Lijin Liu and Honglin Xie and Qiang Fu},
  journal = {Poultry science},
  year = {2026},
  month = oct,
  doi = {10.1016/j.psj.2026.107965},
  url = {https://europepmc.org/article/PMC/PMC13718792},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Fiber-2 induces autolysosome dysfunction and impairs autophagic flux to promote FAdV-4 replication
AU  - Qinqin Sun
AU  - Lianshun Zhang
AU  - Yutong Liu
AU  - Junze Chen
AU  - Siting Zheng
AU  - Lijin Liu
AU  - Honglin Xie
AU  - Qiang Fu
PY  - 2026
DA  - 2026/10/15
JO  - Poultry science
DO  - 10.1016/j.psj.2026.107965
UR  - https://europepmc.org/article/PMC/PMC13718792
AB  - Fowl adenovirus serotype 4 (FAdV-4) causes hepatitis–hydropericardium syndrome in poultry, yet viral subversion of host autophagy remains unclear. Here, we investigated the role of the viral structural protein Fiber-2 in modulating the host autophagy-lysosome pathway. Transcriptomic profiling of LMH cells expressing Fiber-2 revealed coordinated upregulation of autophagy-related genes, validated by quantitative PCR. Functional assays demonstrated that Fiber-2 expression leads to autophagosome accumulation and impaired autophagic flux, as shown by LC3-II/p62 analysis, tandem fluorescent LC3 reporter imaging, Bafilomycin A1 treatment, and transmission electron microscopy. Fiber-2 predominantly localizes to late endosomes and lysosomes, and GFP-Galectin-3 reporter assays indicate that it disrupts lysosomal membrane integrity rather than blocking autophagosome-lysosome fusion. Co-immunoprecipitation (Co-IP) and enrichment analyses identified BECN1, a key autophagy regulator, as a Fiber-2-interacting protein, and associated host proteins were enriched in autophagy-related pathways. Finally, CRISPR/Cas9-mediated deletion of Fiber-2 significantly reduced FAdV-4 replication at later stages of infection, consistent with a proviral role for Fiber-2. These findings indicate that Fiber-2 disrupts autophagic flux by inducing lysosomal dysfunction and membrane damage, thereby promoting FAdV-4 replication and uncovering a previously unrecognized mechanism of viral subversion of host degradative pathways.
SN  - 0032-5791
SN  - 1525-3171
ER  -