Circular RNAs are associated with the resistance to Newcastle disease virus infection in duck cells

Lei Fan; Jinlian Ren; Yinchu Wang; Yiyi Chen; Yichun Chen; Libin Chen; Qiuyan Lin; Ming Liao; Chan Ding; Bin Xiang; Tao Ren

doi:10.3389/fvets.2023.1181916

Circular RNAs are associated with the resistance to Newcastle disease virus infection in duck cells

Front Vet Sci. 2023 Sep 29:10:1181916. doi: 10.3389/fvets.2023.1181916. eCollection 2023.

Authors

Lei Fan^{1

2

3

4}, Jinlian Ren^{1

2

3

4}, Yinchu Wang^{1

2

3

4}, Yiyi Chen^{1

2

3

4}, Yichun Chen^{1

2

3

4}, Libin Chen^{1

2

3

4}, Qiuyan Lin^{1

2

3

4}, Ming Liao⁵, Chan Ding⁶, Bin Xiang⁷, Tao Ren^{1

2

3

4}

Affiliations

¹ College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
² Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou, China.
³ National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou, China.
⁴ Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China.
⁵ Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, China.
⁶ Shanghai Veterinary Research Institute (SHVRI), Chinese Academy of Agricultural Sciences (CAAS), Shanghai, China.
⁷ College of Veterinary Medicine, Yunnan Agricultural University, Kunming, Yunnan, China.

Abstract

Introduction: Newcastle disease virus (NDV) is prevalent worldwide with an extensive host range. Among birds infected with velogenic NDV strains, chickens experience high pathogenicity and mortality, whereas ducks mostly experience mild symptoms or are asymptomatic. Ducks have a unique, innate immune system hypothesized to induce antiviral responses. Circular RNAs (circRNAs) are among the most abundant and conserved eukaryotic transcripts. These participate in innate immunity and host antiviral response progression.

Methods: In this study, circRNA expression profile differences post-NDV infection in duck embryo fibroblast (DEF) cells were analyzed using circRNA transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal significant enrichment of differentially expressed (DE) circRNAs. The circRNA-miRNA-mRNA interaction networks were used to predict the related functions of circRNAs. Moreover, circ-FBXW7 was selected to determine its effect on NDV infection in DEFs.

Results: NDV infection altered circRNA expression profiles in DEF cells, and 57 significantly differentially expressed circRNAs were identified post-NDV infection. DEF responded to NDV by forming circRNAs to regulate apoptosis-, cell growth-, and protein degradation-related pathways via GO and KEGG enrichment analyses. circRNA-miRNA-mRNA interaction networks demonstrated that DEF cells combat NDV infection by regulating cellular pathways or apoptosis through circRNA-targeted mRNAs and miRNAs. circ-FBXW7 overexpression and knockdown inhibited and promoted viral replication, respectively. DEF cells mainly regulated cell cycle alterations or altered cellular sensing to combat NDV infection.

Conclusion: These results demonstrate that DEF cells exert antiviral responses by forming circRNAs, providing novel insights into waterfowl antiviral responses.

Keywords: Newcastle disease virus; antiviral response; circular RNAs; duck embryo fibroblasts; waterfowl.

Grants and funding

This research was funded by the National Natural Science Foundation of China (no. 31902251), the Guangdong Provincial Special Fund for Modern Agriculture Industry Technology Innovation Teams (no. 2022KJ119), the National Natural Science Foundation of China (no. 31872492) and the Special Project on Strategy for Rejuvenation of Guangdong Provincial villages in 2022 (no. 5500-F22039).