title: Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis.
abstract: A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogen-activated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. Next, we found that ALV-J CHN06 strain infection of DF-1 cells correlated with extracellular signal-regulated kinase 2 (ERK2) activation, which was mainly induced within 15 min, a very early stage of infection, and at a late infection stage, from 108 h to 132 h post-infection. Infection with other ALV subgroup (A/B) strains also triggered ERK/MAPK activation. Moreover, when activating ERK2, ALV subgroups A, B and J simultaneously induced the phosphorylation of c-Jun, an AP1 family member and p38 activation but had no obvious effect on JNK activation at either 15 min or 120 h. Interestingly, only PD98059 inhibited the ALV-induced c-Jun phosphorylation while SP600125 or SB203580 had no influence on c-Jun activation. Furthermore, the viral gp85 and gag proteins were found to contribute to ERK2/AP1 activation. Additionally, the specific ERK inhibitor, PD980509, significantly suppressed ALV replication, as evidenced by extremely low levels of ALV promoter activity and ALV-J protein expression. In vivo analysis of ERK2 activation in tumor cells derived from ALV-J-infected chicken demonstrated a strong correlation between ERK/MAPK activation and virus-associated tumorigenesis.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Manman
authors.initials: M
authors.lastname: Dai
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Xiaochan
authors.initials: X
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, People's Republic of China.|Key Laboratory of Veterinary Vaccine Innovation of the Ministry of Agriculture.|South China Collaborative innovation Center for Prevention and Control of poultry Infectious diseases and Safety of Poultry Products.
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, People's Republic of China.|Key Laboratory of Veterinary Vaccine Innovation of the Ministry of Agriculture.|South China Collaborative innovation Center for Prevention and Control of poultry Infectious diseases and Safety of Poultry Products.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Cao
mesh_terms: D000818:Animals; D001354:Avian Leukosis Virus / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D002645:Chickens; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D015683:Gene Products, gag / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D020079:Terminal Repeat Sequences; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases