SOCS3 Promotes ALV-J Virus Replication via Inhibiting JAK2/STAT3 Phosphorylation During Infection.

Guodong Mo,Xiquan Zhang,Zihao Zhang,Qinghua Nie,Ling Lin,Qihong Zhang,Huali Fu,Meiqing Shi,Mingjian Xian,Bowen Hu

doi:10.3389/fcimb.2021.748795

Abstract

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that causes immunosuppression and neoplastic diseases in poultry. Cytokine signal-transduction inhibitor molecule 3 (SOCS3) is an important negative regulator of the JAK2/STAT3 signaling pathway and plays certain roles in ALV-J infection. It is of significance to confirm the roles of SOCS3 in ALV-J infection and study how this gene affects ALV-J infection. In this study, we assessed the expression of the SOCS3 gene in vivo and in vitro, and investigated the roles of SOCS3 in ALV-J infection using overexpressed or interfered assays with the SOCS3 in DF-1 cells. The results showed that the SOCS3 expression of ALV-J infected chickens was different from uninfected chickens in the spleen, thymus and cecal tonsil. Further, SOCS3 is mainly expressed in the nucleus as determined by immunofluorescence assay. Overexpression of SOCS3 in DF-1 cells promoted the replication of ALV-J virus, and the expression of interferons (IFNα and INFβ), inflammatory factors (IL-6 and TNFα) along with interferon-stimulating genes (CH25H, MX1, OASL, and ZAP). Conversely, interference of SOCS3 showed the opposite results. We also observed that SOCS3 promoted ALV-J virus replication by inhibiting JAK2/STAT3 phosphorylation. In conclusion, SOCS3 promotes ALV-J replication via inhibiting the phosphorylation of the JAK2/STAT3 signaling pathway. These results would advance further understanding of the persistent infection and the viral immune evasion of the ALV-J virus.

Highlights

Avian leukemia virus subgroup J was first isolated and identified from commercial broilers in 1988, which mainly causes myeloid leukosis (Payne et al, 1991; Payne et al, 1992)
We further found that the SOCS3 gene was one of the differentially expressed genes based on the RNA-seq data (PRJNA552417) of spleen tissues from 7 days-old chicken infected with Avian leukosis virus subgroup J (ALV-J)
Since SOCS3 plays an important role via the JAK/STAT signaling pathway (Chen et al, 2000; Rawlings et al, 2004), we further evaluated the expression of JAK2 and STAT3 genes in ALV-J infected and uninfected tissues and cells to study how SOCS3 promotes ALV-J virus replication

Summary

Introduction

Avian leukemia virus subgroup J was first isolated and identified from commercial broilers in 1988, which mainly causes myeloid leukosis (Payne et al, 1991; Payne et al, 1992). We performed RNA-seq on chicken primary monocyte-derived macrophages (MDM) cells infected with ALV-J. The results revealed that the cytokine signal transduction inhibitor 3 (SOCS3) was a differentially expressed gene in the JAK/STAT signaling pathway (Feng et al, 2019). We further found that the SOCS3 gene was one of the differentially expressed genes based on the RNA-seq data (PRJNA552417) of spleen tissues from 7 days-old chicken infected with ALV-J (data unpublished). Overexpression of SOCS3 in MDM cells promotes ALV-J virus replication (Feng et al, 2019). These observations imply that SOCS3 may play an important role in ALV-J virus replication in chickens

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Results

Conclusion