Characterization of TCRβ and IGH Repertoires in the Spleen of Two Chicken Lines with Differential ALV-J Susceptibility Under Normal and Infection Conditions

Animals, Journal Year: 2025, Volume and Issue: 15(3), P. 334 - 334

Published: Jan. 24, 2025

This study investigates the immunological factors underlying differential susceptibility of two chicken strains, E- and M-lines, to avian leukosis virus subgroup J (ALV-J). During eradication at a breeder farm in Guangdong, we observed strain-specific differences ALV-J. Moreover, E-line chickens exhibited slower antibody response ALV-J compared M-line chickens. As T cell receptor (TCR) B (BCR) are critical for antigen recognition, their activation triggers specific immune responses, including production. Using high-throughput sequencing, characterized beta (TCRβ) immunoglobulin heavy chain (IGH) repertoires spleen tissues from both strains. The demonstrated higher clonal diversity TCRβ IGH under normal conditions E-line, suggesting broader baseline recognition capacity. Following infection, repertoire remained unchanged, while displayed distinct expansion patterns complementarity-determining region 3 (CDR3) length distributions between lines, potentially affecting ability recognize antigens. Our provides first comprehensive comparison dynamics with different susceptibilities, offering new insights into molecular mechanisms resistance

Language: Английский

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Rapid adaptive evolution of avian leukosis virus subgroup J in response to biotechnologically induced host resistance

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012468 - e1012468

Published: Aug. 15, 2024

Genetic editing of the germline using CRISPR/Cas9 technology has made it possible to alter livestock traits, including creation resistance viral diseases. However, virus adaptability could present a major obstacle in this effort. Recently, chickens resistant avian leukosis subgroup J (ALV-J) were developed by deleting single amino acid, W38, within ALV-J receptor NHE1 genome editing. This was confirmed both vitro and vivo . In W38 -/- chicken embryonic fibroblasts all tested strains shown. To investigate capacity for further adaptation, we used retrovirus reporter-based assay select adapted variants. We assumed that adaptive mutations overcoming cellular would occur envelope protein. accordance with assumption, isolated sequenced numerous variants found their genes eight independent nucleotide substitutions. confirm these substitutions, introduced them into original reporter. All replicated effectively while , sensitive tumor induction two Importantly, alleles more extensive modifications have remained virus. These results demonstrate an important strategy engineering towards antivirus illustrate induced minor can be overcome conclude complex will necessary attain robust resistance.

Language: Английский

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Autophagy-mediated TET2 degradation by ALV-J Env protein suppresses innate immune activation to promote viral replication

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

ABSTRACT Avian leukosis virus subgroup J (ALV-J) poses a significant threat to the poultry industry; yet, our understanding of its replication and pathogenic mechanisms is limited. The Ten-Eleven Translocation 2 (TET2) an indispensable regulatory factor in active DNA demethylation immune response regulation. This study reports time-dependent decrease TET2 levels following ALV-J infection shows that reduction protein mediated by autophagy pathway. Mechanistically, we found accumulation Env at late stages triggers autophagy, which, turn, causes be exported from nucleus subsequently degraded cytoplasm. Using CRISPR-Cas9 technology, generated TET2-deficient chicken macrophages exhibited increased susceptibility replication, which was reversed overexpression. In addition, transcriptome analysis revealed absence impairs expression numerous cytokines innate immune-related genes, particularly those downregulated genes enriched RIG-I Toll-like signaling pathways, leading enhanced vitro . summary, research identifies as restriction factor. However, exploits machinery promote degradation protein, thereby disrupting host’s responses for viral replication. IMPORTANCE carcinogenic retrovirus plays critical role avian leukosis, primarily affecting chickens. Infection with leads decreased production performance, compromised function, development tumors, such myelocytoma. Currently, there are no effective treatments ALV-J, making control outbreaks challenge severe economic consequences industry. has been implicated virus’s pathogenicity. Our induces host cells through autophagic TET2, key epigenetic regulator. loss results downregulation gene expression, promoting first report elucidate suppression via during infection, providing new insights into evasion.

Language: Английский

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N6-methyladenosine modification of the subgroup J avian leukosis viral RNAs attenuates host innate immunity via MDA5 signaling

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1013064 - e1013064

Published: April 8, 2025

Subgroup J avian leukosis virus (ALV-J), a retrovirus, elicits immunosuppression and persistent infections in chickens. Although it is widely acknowledged that ALV-J can evade the host’s innate immune defenses, mechanisms behind this evasion remain elusive. N6-methyladenosine (m 6 A), most prevalent internal RNA modification, plays role evasion. Our research identified as an inefficient stimulator of immunity vitro vivo , with its genomic featuring m A modifications predominantly envelope protein ( Env) region 3′ untranslated 3 ′ UTR ). To elucidate functional consequences we subsequently generated A-deficient through culturing DF-1 overexpressing fat mass obesity-associated (FTO) cells. The virus, or RNAs significantly enhanced IFN- β production compared to wild-type (wt) ALV-J, suggesting pivotal regulatory function modulating response. Mechanistically, modification directly impacted recognition by MDA5, weakening binding ubiquitination attenuating IFN-β activation. Moreover, created inducing mutations sites within Env exhibited reduced replication capacity elevated expression host Importantly, phenomenon was abolished MDA5-knockout cells, further demonstrating core MDA5. These data demonstrate dampens response MDA5 signaling pathway.

Language: Английский

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Isolation and molecular characteristic of subgroup J avian leukosis virus in Guangxi and Jiangsu provinces of China during 2022-2023

Poultry Science, Journal Year: 2025, Volume and Issue: unknown, P. 105272 - 105272

Published: May 1, 2025

Language: Английский

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Identification of Cables1 as a critical host factor that promotes ALV-J replication via genome-wide CRISPR/Cas9 gene knockout screening

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107804 - 107804

Published: Sept. 1, 2024

Language: Английский

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RNA-Seq Analysis of Glycolysis Regulation of Avian Leukosis Virus Subgroup J Replication

Animals, Journal Year: 2024, Volume and Issue: 14(17), P. 2500 - 2500

Published: Aug. 28, 2024

Avian Leukosis virus (ALV) is a widely spread that causes major economic losses to the global poultry industry. This study aims investigate effect of glycolysis on replication ALV-J and identify key circular RNAs regulate virus. We found glucose uptake, pyruvate content, lactate content in DF1 cells were increased after infection. Moreover, inhibiting ALV-J-infected reduced To further mechanism virus, we performed RNA-seq treated with inhibition. results show total 10,375 (circRNAs) identified, which main types exonic RNAs, 28 circRNAs differentially expressed between Then, functional enrichment analysis circRNA source target genes. Functional indicated some might be involved regulating by influencing pathways like glycolysis/gluconeogenesis, NOD-like receptor signaling pathway, MAPK p53 Toll-like Insulin Apoptosis. revealed its possible regulatory mechanism, provided basis for understanding factors reducing rate infection poultry.

Language: Английский

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Advances on ALV-J in China over the past two decades

Journal of Integrative Agriculture, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Avian leukosis is an important tumorigenic disease caused by the avian virus (ALV) in poultry. ALVs belong to retroviral family and are classified into 11 subgroups (ALV-A ALV-K). Among them, ALV-J was first introduced China 1999, spreading widely evolving from infecting meat-type chickens layer Chinese local chickens. typically induces myeloid infected chickens, but also a high proportion of hemangiomas posing serious threat poultry breeds China. As retrovirus, genome has undergone significant mutations, which may be related expansion infection host range increased pathogenicity ALV-J. Over last two decades, introduction spread have substantial losses industry. Specialized detection assays been developed combat infections Additionally, ongoing research aims employ gene-editing technology as novel antiviral strategy control ALV infections. This review highlights importance understanding impact on industry emphasizes need for innovation safeguard health promote sustainable farming practices

Language: Английский

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