ACSL1 Inhibits ALV-J Replication by IFN-Ⅰ Signaling and PI3K/Akt Pathway.

Qihong Zhang,Guodong Mo,Ling Lin,Tingting Xie,Zihao Zhang,Xiquan Zhang

doi:10.3389/fimmu.2021.774323

Qihong Zhang, Guodong Mo + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2021.774323

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Journal: Frontiers in Immunologie	Publication Date: Oct 29, 2021
Citations: 14	License type: CC BY 4.0

Affiliation: South China Agricultural University

Abstract

J subgroup avian leukosis virus (ALV-J) infection causes serious immunosuppression problems, leading to hematopoietic malignancy tumors in chicken. It has been demonstrated that interferon-stimulated genes (ISGs) could limit ALV-J replication; nevertheless, the underlying mechanisms remain obscure. Here, we demonstrate that Long-chain Acyl-CoA synthetase 1 (ACSL1) is an interferon (IFN)-stimulated gene that specifically restricts the replication of ALV-J due to the higher IFN-I production. More importantly, ACSL1 induces primary monocyte-derived macrophages (MDMs) to pro-inflammatory phenotypic states during ALV-J infection, and ACSL1 mediates apoptosis through the PI3K/Akt signaling pathway in ALV-J-infected primary monocyte-derived macrophages (MDMs). Overall, these results provide evidence that ACSL1 contributes to the antiviral response against ALV-J.

Highlights

J subgroup avian leukosis virus (ALV-J) is an alpharetro virus that mainly induces hematopoietic malignancy with myeloid leukemia in chicken [1, 2]
Through exogenous expression and small interfering RNA knockdown, we find that ACSL1 inhibits ALV-J replication by enhancing IFN-I production
To identify whether ACSL1 was an IFN-stimulated genes (ISGs), we examined the levels of ACSL1 in DF-1 cells or monocyte-derived macrophages (MDMs) infected with ALV-J or stimulated with IFN-a

Summary

Introduction

J subgroup avian leukosis virus (ALV-J) is an alpharetro virus that mainly induces hematopoietic malignancy with myeloid leukemia in chicken [1, 2]. The innate immune system is the first line of host defense against pathogen invasion [6]. The ISGs play crucial roles and exert diverse functions at multiple levels of antiviral immunity. The interferon-induced transmembrane (IFITM) family blocks virus replication by inhibiting the virus and host cell membrane fusion [8], the zinc-finger antiviral protein (ZAP) binds to the target RNA to block the translation of viral mRNA [9], and the IFNinduced protein with tetratricopeptide repeats 5 (IFIT5) inhibits RNA virus replication by preventing virus translation and initiating innate immunity [10, 11].

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