Recent advances in enterovirus A71 infection and antiviral agents.

Enterovirus A71 (EV-A71) is one of the major causative agents of hand-foot-and-mouth disease (HFMD) that majorly affects children. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death. HFMD caused by EV-A71 has emerged as an acutely infectious disease of highly pathogenic potential in the Asia-Pacific region. In this review, we introduced the properties and life cycle of EV-A71, the pathogenesis and the pathophysiology of EV-A71 infection, including: tissue tropism and host range of virus infection, the diseases caused by the virus, as well as the genes and host cell immune mechanisms of major diseases caused by EV71 infection, such as encephalitis and neurological pulmonary edema. At the same time, clinicopathological characteristics of EV71 infection were introduced. There is currently no specific medication for EV-A71 infection, highlighting the urgency and significance of developing suitable anti-EV-A71 agents. This overview also summarizes the targets of existing anti-EV-A71 agents, including virus entry, translation, polyprotein processing, replication, assembly and release; interferons (IFNs); interleukin (IL); the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) signaling pathways; the oxidative stress pathway; and the ubiquitin-proteasome system, et al. Furthermore, it overviews the effects of natural products, monoclonal antibodies, and RNA interference against EV-A71. It also discusses issues limiting the research of antiviral drugs. This review is a systematic and comprehensive summary of the mechanism and pathological characteristics of EV71 infection, the latest progress of existing anti-EV-A71 agents. It would provide better understanding and guidance for the research and application of EV71 infection and antiviral inhibitors.