Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis.

Manman Dai,Xiaochan Wu,Min Feng,Weisheng Cao,Ming Liao,Di Liu,Yu Ye

doi:10.1038/srep19226

Manman Dai, Xiaochan Wu + Show 5 more

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https://doi.org/10.1038/srep19226

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Journal: Scientific Reports	Publication Date: Jan 12, 2016
Citations: 58	License type: CC BY 4.0

Affiliation: South China Agricultural University

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.

Highlights

A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogenactivated protein kinase (MAPK) signal transduction pathway in DF-1 cells after Avian leukosis viruses (ALV) subgroup J (ALV-J) infection
Given the significant correlation between the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway and tumorigenesis, we initially investigated whether ALV subgroup J (ALV-J) strain CHN06 leads to activation of this pathway during the infection process
These results suggest that ALV-J-induced activation of the MAPK pathway occurred mainly at the early and late infection stages

Summary

Introduction

A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogenactivated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. 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. Mitogen-activated protein kinase[1] (MAPK) which is closely related to ERK/MAPK signaling pathway may play a role in ALV-J propagation, cell proliferation and neoplasm formation. MAPK cascades are composed of four prototype members, the extracellular signal-regulated kinase (ERK) 1/2, p38, the Jun-N-terminal kinase (JNK/SAPK) and ERK5, which are key signaling pathways in the control of cell proliferation, differentiation, apoptosis and immune responses[9,10,11,12]. C-Jun has been implicated in events leading to tumor development[15,16,17,18]

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