title: MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication.
abstract: Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 (MDA5) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed thatMDA5is a direct target of miR-34b-5p.In vitro, overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression ofMDA5inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown ofMDA5promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections,MDA5can detect virus invasion and it triggers the MDA5 signaling pathway.MDA5overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-Jenvgene and it can suppress virion secretion. In contrast, in response to the knockdown ofMDA5by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated (P< 0.05), but the mRNA and protein expression of ALV-Jenvand the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targetsMDA5to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway.
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Bahareldin Ali
authors.initials: BA
authors.lastname: Abdalla
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Nie
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of AgricultureGuangzhou, China.
authors.forename: Xiquan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001354:Avian Leukosis Virus / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002645:Chickens; D054884:Host-Pathogen Interactions; D000072640:Interferon-Induced Helicase, IFIH1 / Q000037:antagonists & inhibitors*; D035683:MicroRNAs / Q000378:metabolism*; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Avian leukosis virus subgroup J (ALV-J); Cell proliferation; MDA5 signaling pathway; MiR-34b-5p; melanoma differentiation-associated gene 5 (MDA5)