Innate Immunity and Immune Evasion by Enterovirus 71

Abstract

Enterovirus 71 (EV71) is a major infectious disease affecting millions of people worldwide and it is the main etiological agent for outbreaks of hand foot and mouth disease (HFMD). Infection is often associated with severe gastroenterological, pulmonary, and neurological diseases that are most prevalent in children. Currently, no effective vaccine or antiviral drugs exist against EV71 infection. A lack of knowledge on the molecular mechanisms of EV71 infection in the host and the virus-host interactions is a major constraint to developing specific antiviral strategies against this infection. Previous studies have identified and characterized the function of several viral proteins produced by EV71 that interact with the host innate immune proteins, including type I interferon signaling and microRNAs. These interactions eventually promote efficient viral replication and increased susceptibility to the disease. In this review we discuss the functions of EV71 viral proteins in the modulation of host innate immune responses to facilitate viral replication.

Keywords: Enterovirus 71; Interferon antagonist; J0101; innate immunity.

Figure 1

Diagrammatic representation of the EV71 genome and polyprotein products. Cap independent IRES driven protein translation produce a single polyprotein followed by proteolytic cleavage into partially processed products and eleven mature products. Virus encoded 3C and 2A proteases are accountable for this polyprotein processing at different stages.

Figure 2

A graphical illustration of EV71 evasion strategies in cellular signaling pathways. EV71 3Cpro, 2Apro, and 2C are mainly involved in down-regulation of type I IFN, pro-inflammatory cytokines and ISGs induction at different stages. The interacting cellular signaling molecules with different viral proteins are indicated at each level. (MDA5: Melanoma-differentiation-associated protein5, RIG-I: Retinoic acid-inducible gene 1, MAVS: Mitochondrial antiviral-signaling protein, TBK1:TANK-binding kinase 1, IRF3/7:Interferon Regulatory Factor 3/7, TRIF: TIR-domain-containing adapter-inducing interferon-β, TLR: Toll-like receptors, DAMPs: Danger associated molecular patterns, eIFG4: eukaryotic translation initiation factor 4G, TRAF6: TNF receptor-associated factor 6, TAK1:Transforming growth factor-β activated kinase 1, TAB2/3: TGF-β Activated Kinase 2/3, IFNAR: Interferon-α/β receptor, TAK1: Janus kinase 1, TYK2: Tyrosine Kinase 2, STAT1/2: Signal transducer and activator of transcription 1/2, ISG: interferon-stimulated genes, ISRE: Interferon-sensitive response element, IFNs: Interferons).