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.

The role of miR‐146a in viral infection

“…Excessive pro‐inflammatory chemokine and cytokine responses contribute to the EV71 infection severity. Also, this infection does not promote IFN‐I production . Ho and colleagues showed that EV71 infection‐promoted miR‐146a expression leads to suppress IFN production through inhibition of TRAF6 and IRAK1, two key factors implicated in TLR signaling pathways and IFN production .…”

Enterovirus 71 inhibits cellular type I interferon signaling by inhibiting host RIG-I ubiquitination

“…EV71 causes HFMD, neurological complications or even fatal diseases in young children and infants [5,8]. Its pathogenicity is likely related to its ability to evade host innate immunity [18,19].…”

“…These IFNs are essential in the early control of virus infection as they facilitate the induction of over 300 ISGs that degrade viral RNAs and induce apoptosis, resulting in an antiviral state in the microenvironment [8,9]. Previous studies showed that type I IFN had a protective role in EV71 pathogenesis.…”

“…However, EV71 has evolved many different mechanisms for evading the type-I IFN response to prevent their clearance. The 3C and 2A proteases of EV71 played a dominant defensive role against host innate immunity by cleaving and binding to different antiviral signaling molecules [8]. EV71 3C protein not only inhibited IFN-b expression by targeting the adaptor RIG-I [19], but also cleaved the TRIF [18], IRF3, IRF7 [14], and TAK1/TAB1/TAB2/TAB3 complex [16].…”

“…The outbreaks and severity of EV71 infection have been frequently reported worldwide, and recently EV71 has become a major threat to public health in China [6,7]. Recent studies show that EV71 pathogenesis and prevalence are caused by the evasion of innate immune surveillance [8].…”