Contents lists available at ScienceDirect Virus Research journal homepage: www.elsevier.com/locate/virusres Review Anti-chicken type I IFN countermeasures by major avian RNA viruses Faisal Rasheed Anjum a,1 , Sidra Anam a,1 , Sajjad ur Rahman a , Sultan Ali a , Muhammad Aamir Aslam a , Farzana Rizvi b , Muhammad Asif a , Rana Muhammad Abdullah a , Muhammad Abaidullah c , Muhammad Zulqarnain Shakir a , Mohsan Ullah Goraya a, * a Institute of Microbiology, University of Agriculture, Faisalabad, Pakistan b Department of Pathology, Faculty of Veterinary Science, University of Agriculture, Faisalabad, Pakistan c Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China ARTICLE INFO Keywords: Chicken type I interferons Virus-host interactions Innate immune evasion Avian RNA viruses ABSTRACT Chicken type I interferons (type I IFNs) are key antiviral players of the chicken innate immune system and are considered potent antiviral agents against avian viral pathogens. Chicken type I IFNs are divided into three subtypes namely, chIFN-α, chIFN-β, and chIFN-κ. Viral pathogen-associated molecular patterns (PAMPs) re- cognized by their corresponding specific PRRs (pattern recognition receptors) induce the expression of chicken type I IFNs. Interaction of chicken type I IFNs with their subsequent IFN receptors results in the activation of the JAK-STAT pathway, which in turn activates hundreds of chicken interferon-stimulated genes (chISGs). These chISGs establish an antiviral state in neighboring cells and prevent the replication and dissemination of viruses within chicken cells. Chicken type I IFNs activate different pathways that constitute major antiviral innate defense mechanisms in chickens. However, evolutionary mechanisms in viruses have made them resistant to these antiviral players by manipulating host innate immune pathways. This review focuses on the underlying molecular mechanisms employed by avian RNA viruses to counteract chicken type I IFNs and chISGs through different viral proteins. This may help to understand host-pathogen interactions and the development of novel therapeutic strategies to control viral infections in poultry. 1. Introduction Recognition of viral pathogens by host pattern recognition receptors (PRRs) initiates a cascade of intracellular signaling events, which lead to the engagement of specific molecules involved in the antiviral re- sponse to protect the host cells (Goraya et al., 2019). One of the most potent events is the activation of interferon induction pathway (Fensterl and Sen, 2009)(Maarouf et al., 2018). Interferons (IFNs), a family of cytokines, are important elements in provoking innate immune re- sponses against viruses. Recognition of a viral antigen by PRRs induces type I, type II, and type III IFNs (Chen et al., 2018; Goraya et al., 2019). Generally, PRRs [Retinoic acid-inducible gene-1 (RIG-1) e.g., helicases (RLH), toll-like receptors (TLRs), and DNA sensors] are in- volved in the expression of type I IFNs (Chen et al., 2018). The RIG-I that senses 5′-triphosphate containing RNA and induces early cytokines in response to viral infection are absent in chickens (Yoneyama et al., 2004)(Hornung et al., 2006; Karpala et al., 2011). However, even in the absence of RIG-I, chicken cells mount a potent type I IFN response against RNA viruses most probably due to chicken melanoma differ- entiation-associated gene 5 (chMDA5) and Chicken Laboratory of Ge- netics and Physiology 2 (chLGP2). The ChMDA5 is a stem binder of dsRNA that can recognize both short and long dsRNA and is important in innate sensing of avian viruses (Chen et al., 2016; Hayashi et al., 2014; Kato et al., 2006; Liniger et al., 2012b; Uchikawa et al., 2016). https://doi.org/10.1016/j.virusres.2020.198061 Received 17 February 2020; Received in revised form 27 April 2020; Accepted 10 June 2020 Abbreviations: IFN, interferon; chIFN, chicken IFN; PAMPs, pathogen associated molecular patterns; PRRs, pattern recognition receptors; TLRs, toll like receptors; chTLRs, chicken TLRs; RIG-I, Retinoic acid inducible gene-I; RLH, RIG-I like helicases; MDA5, melanoma differentiation-associated gene 5; chMDA5, chicken MDA5; LGP2, Laboratory of Genetic and Physiology 2; AIM2, absent in melanoma 2; chIRF7, chicken IFN regulatory factor 7; chIRF1, chicken IFN regulatory factor 1; AP-1, activated protein-1; ISGs, IFN stimulated genes; chISGs, chicken ISGs; AIV, avian influenza virus; IBDV, infectious Bursal disease virus; NDV, Newcastle disease virus; JAK, Janus kinase; STAT, transducer and activator of transcription; OAS, oligoadenylate synthetase; ChOAS, chicken OAS; TRIF, TLR domain containing adaptor inducing IFN-β; Myd88, myeloid differentiation primary response 88; STING, Stimulator of IFN genes; chSTING, chicken STING; MAVS, mitochondrial antiviral- signaling protein; DDX41, DEAD (Asp-Glu-Ala-Asp) box polypeptide 4; chDDX41, chicken DDX41; pSTAT1, phospho-STAT1 ⁎ Corresponding author at: Institute of Microbiology, Faculty of Veterinary Science, University of Agriculture, Faisalabad, 38000, Pakistan. E-mail address: goraya_uaf@yahoo.com (M.U. Goraya). 1 Both authors contributed equally to this work. Virus Research 286 (2020) 198061 Available online 16 June 2020 0168-1702/ © 2020 Elsevier B.V. All rights reserved. T