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Distribution of enterovirus 71 RNA in inflammatory cells infiltrating different tissues in fatal cases of hand, foot, and mouth disease

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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.

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Abbreviations

EV71:

Enterovirus 71

HFMD:

Hand, foot, and mouth disease

CNS:

Central nervous system

ISH:

In situ hybridization

IHC:

Immunohistochemistry

FFPE:

Formalin-fixed, paraffin-embedded

CD:

Cluster of differentiation

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Acknowledgments

This work was supported by the National Natural Science Foundation of China [81171631], the National Basic Research Program of China [973 Program, 2011CB504903], the National Science and Technology Major Projects [2012ZX10004501], and the National Science and Technology Major Projects of Therapy [2012ZX10004301-008].

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. 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, Bei**g, 100021, China

    Pin Yu, Linlin Bao, Lili Xu, Wei Deng, Yanfeng Xu, Yanfeng Yao, Fengdi Li, Qi Lv & Chuan Qin

  2. Department of Pathology, Peking University Health Science Center, Bei**g, 100191, China

    Zifen Gao

  3. Department of Pathology, Shandong Provincial Hospital affiliated with Shandong University, **an, 250021, China

    Yuanyuan Zong

  4. Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Bei**g, 100044, China

    Zhancheng Gao

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  1. Pin Yu
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  2. Zifen Gao
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  3. Yuanyuan Zong
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  4. Linlin Bao
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  9. Yanfeng Yao
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  11. Qi Lv
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  12. Chuan Qin
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Corresponding author

Correspondence to Chuan Qin.

Additional information

P. Yu, Z. Gao and Y. Zong contributed equally to this work.

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Yu, P., Gao, Z., Zong, Y. et al. Distribution of enterovirus 71 RNA in inflammatory cells infiltrating different tissues in fatal cases of hand, foot, and mouth disease. Arch Virol 160, 81–90 (2015). https://doi.org/10.1007/s00705-014-2233-x

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  • DOI: https://doi.org/10.1007/s00705-014-2233-x

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