GADD45β, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens.

Xinheng Zhang,Zhenkai Dai,Xinjian Li,Yiming Yan,Jingyun Ma,Zhuanqiang Yan,Piaopiao Lu,Huanmin Zhang,Feng Chen,Qingmei Xie,Wencheng Lin,Weiguo Chen

doi:10.18632/oncotarget.12027

Abstract

Avian leukosis virus subgroup J (ALV-J) is a retroviruses that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that promote resistance to ALV-J infection in chickens, we bred ALV-J resistant and susceptible chickens (F3 generation). RNA-sequencing (RNA-Seq) of liver tissue from the ALV-J resistant and susceptible chickens identified 216 differentially expressed genes; 88 of those genes were up-regulated in the ALV-J resistant chickens (compared to the susceptible ones). We screened for significantly up-regulated genes (P < 0.01) of interest in the ALV-J resistant chickens, based on their involvement in biological signaling pathways. Functional analyses showed that overexpression of GADD45β inhibited ALV-J replication. GADD45β could enhance defense against ALV-J infection and may be used as a molecular marker to identify ALV-J infections.

Highlights

Avian leukosis viruses (ALVs) are species of the Alpharetrovirus genus [1, 2]
Chickens in the A, E, and F lines were more resistant to Avian leukosis virus subgroup J (ALV-J); the positive rates of infection with ALV-J in the A, E, and F lines were 16.49% (16/97), 36.84% (35/95), and 35.79% (34/95), respectively
The livers of ALV-J resistant chickens were normal, while livers of susceptible chickens showed swollen lesions, hemorrhagic spots and white nodules, livers of susceptible chickens were found to be positive for infection by indirect immunofluorescent assay (IFA) (Figure 1)

Summary

Introduction

Avian leukosis viruses (ALVs) are species of the Alpharetrovirus genus (family: Retroviridae) [1, 2]. Six subgroups of ALV are known in chickens, referred to as ALV-A, -B, -C, -D, -E, and -J. ALV-J is an oncogenic exogenous retrovirus of chickens; it was first reported in the United Kingdom in 1991, and has subsequently caused severe economic losses in the poultry industry worldwide [3, 4]. Hosts with clinical ALV-J infections develop of a variety of tumors, including myelocytomas, sarcomas, hemangiomas, nephromas and erythroblastosis and have the characteristic of delayed growth, high mortality, and immune tolerance [5, 6, 7, 8]. The control and eradication of ALV-J from pedigree generations has become a priority in the primary breeder industry [10]

Methods

Results

Conclusion