title: Distribution of enterovirus 71 RNA in inflammatory cells infiltrating different tissues in fatal cases of hand, foot, and mouth disease.
abstract: In previous studies of hand, foot, and mouth disease patients fatally infected with enterovirus 71 (EV71), the distribution of viral protein, but not the genome, was determined. To understand the pathogenesis of EV71, however, it is important to investigate the spread of the viral genome. There have been no pathological studies of in situ EV71 viral RNA in inflammatory cells infiltrating various tissues of fatal cases. We therefore first investigated the distribution and classification of inflammatory cells in various tissues and then performed in situ EV71 RNA hybridization in these tissues to better understand the pathogenesis of EV71 infection. EV71 RNA was found mainly in inflammatory cells infiltrating the central nervous system (CNS), intestines, lungs, and tonsils. Most EV71 RNA-positive inflammatory cells in the CNS were macrophages/microglia and neutrophils infiltrating the perivascular cuffing, microglial nodule, neuronophagia, and meninges. CD68+ macrophages and CD15+ neutrophils were diffusely distributed in tissues with severe pathological changes. This study demonstrates the presence of EV71 RNA in inflammatory cells infiltrating tissues in fatally infected patients. Our findings suggest that fatal EV71 infection with extensive infiltration of macrophages/microglia and neutrophils into the CNS results in severe neurological lesions.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, 100021, China, pinyucau@gmail.com.
authors.forename: Pin
authors.initials: P
authors.lastname: Yu
authors.forename: Zifen
authors.initials: Z
authors.lastname: Gao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zong
authors.forename: Linlin
authors.initials: L
authors.lastname: Bao
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhancheng
authors.initials: Z
authors.lastname: Gao
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yao
authors.forename: Fengdi
authors.initials: F
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D029821:Enterovirus A, Human / Q000302:isolation & purification*; D016679:Genome, Viral; D006232:Hand, Foot and Mouth Disease / Q000401:mortality / Q000821:virology*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D017403:In Situ Hybridization; D007249:Inflammation / Q000821:virology*; D012367:RNA, Viral / Q000302:isolation & purification*; D014018:Tissue Distribution
chemical_list: D012367:RNA, Viral