Dysregulated autophagy contributes to the pathogenesis of enterovirus A71 infection
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Cell & Bioscience Open Access
REVIEW
Dysregulated autophagy contributes to the pathogenesis of enterovirus A71 infection Chuanjie Zhang1, Yawei Li2 and Jingfeng Li3*
Abstract Enterovirus A71 (EVA71) infection continues to remain a vital threat to global public health, especially in the Asia– Pacific region. It is one of the most predominant pathogens that cause hand, foot, and mouth disease (HFMD), which occurs mainly in children below 5 years old. Although EVA71 prevalence has decreased sharply in China with the use of vaccines, epidemiological studies still indicate that EVA71 infection involves severe and even fatal HFMD cases. As a result, it remains more fundamental research into the pathogenesis of EVA71 as well as to develop specific antiviral therapy. Autophagy is a conserved, self-degradation system that is critical for maintaining cellular homeostasis. It involves a variety of biological functions, such as development, cellular differentiation, nutritional starvation, and defense against pathogens. However, accumulating evidence has indicated that EVA71 induces autophagy and hijacks the process of autophagy for their optimal infection during the different stages of life cycle. This review provides a perspective on the emerging evidence that the “positive feedback” between autophagy induction and EVA71 infection, as well as its potential mechanisms. Furthermore, autophagy may be involved in EVA71-induced nervous system impairment through mediating intracranial viral spread and dysregulating host regulator involved self-damage. Autophagy is a promising therapeutic target in EVA71 infection. Keywords: Autophagy, Enterovirus A71 (EVA71), Nervous system injury, Pathogenesis, Hand, foot, and mouth disease (HFMD) Introduction Enterovirus A71 (EVA71) is a small, non-enveloped, icosahedral-shaped, positive-sense, single-stranded RNA virus belonging to the enterovirus, family Picornaviridae. EVA71 was first isolated from infants suffering from central nervous system (CNS) diseases in California in 1969 [1]. The first outbreak of EVA71 was reported in Bulgaria in 1975 [2], followed by rapid spreading worldwide. EVA71 infection has been reported to be prevalent in Asia–Pacific regions since the late 1990s [3]. EVA71 is one of the most common etiologic agents that cause hand, foot, and mouth disease (HFMD), which is a highly contagious disease around the world *Correspondence: [email protected] 3 Department of Pediatrics, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, People’s Republic of China Full list of author information is available at the end of the article
predominantly affecting children under the age of five [4]. HFMD has been classified as a notably infectious disease in category III since 2008 in China. During the past decade, a cumulative number of 20,537,199 HFMD cases, including 3667 deaths, have been reported by the Chinese Center for Disease Control and Prevention (China CDC). The symptoms of HFMD are usually mild. However, the neurological and cardiorespiratory complications
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