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Am J Pathol. 2014 Mar;184(3):714-20. doi: 10.1016/j.ajpath.2013.11.009. Epub 2013 Dec 27.

Tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in EV71 encephalomyelitis.

Author information

1
Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China.
2
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
3
Department of Pathology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York.
4
Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: wongkt@ummc.edu.my.
5
Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China. Electronic address: lumin@hsc.pku.edu.cn.

Abstract

Enterovirus 71 (EV71; family Picornaviridae, species human Enterovirus A) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. We investigated extra-central nervous system (extra-CNS) tissues capable of supporting EV71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor B2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL-1). Formalin-fixed, paraffin-embedded CNS and extra-CNS tissues from seven autopsy cases were examined by IHC and in situ hybridization to evaluate viral antigens and RNA. Viral receptors were identified with IHC. In all seven cases, the CNS showed stereotypical distribution of inflammation and neuronal localization of viral antigens and RNA, confirming the clinical diagnosis of EV71 encephalomyelitis. In six cases in which tonsillar tissues were available, viral antigens and/or RNA were localized to squamous epithelium lining the tonsillar crypts. Tissues from the gastrointestinal tract, pancreas, mesenteric nodes, spleen, and skin were all negative for viral antigens/RNA. Our novel findings strongly suggest that tonsillar crypt squamous epithelium supports active viral replication and represents an important source of viral shedding that facilitates person-to-person transmission by both the fecal-oral or oral-oral routes. It may also be a portal for viral entry. A correlation between viral infection and SCARB2 expression appears to be more significant than for PSGL-1 expression.

PMID:
24378407
DOI:
10.1016/j.ajpath.2013.11.009
[Indexed for MEDLINE]

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