title: Human astrocytic cells support persistent coxsackievirus B3 infection.
abstract: Enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. Although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. Here, we investigated the susceptibility of three human brain cell lines, CCF-STTG1, T98G, and SK-N-SH, to infection with three enterovirus serotypes: coxsackievirus B3 (CVB3), enterovirus 71, and coxsackievirus A9. Persistent infection was observed in CVB3-infected CCF-STTG1 cells, as evidenced by prolonged detection of infectious virions, viral RNA, and viral antigens. Of note, infected CCF-STTG1 cells expressed the nonfunctional canonical viral receptors coxsackievirus-adenovirus receptor and decay-accelerating factor, while removal of cell surface chondroitin sulfate from CCF-STTG1 cells inhibited the replication of CVB3, suggesting that receptor usage was one of the major limiting factors in CVB3 persistence. In addition, CVB3 curtailed the induction of beta interferon in infected CCF-STTG1 cells, which likely contributed to the initiation of persistence. Furthermore, proinflammatory chemokines and cytokines, such as vascular cell adhesion molecule 1, interleukin-8 (IL-8), and IL-6, were upregulated in CVB3-infected CCF-STTG1 cells and human progenitor-derived astrocytes. Our data together demonstrate the potential of CCF-STTG1 cells to be a novel cell model for studying CVB3-central nervous system interactions, providing the basis toward a better understanding of CVB3-induced chronic neuropathogenesis.
authors.affiliation: Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zheng
authors.forename: Bo
authors.initials: B
authors.lastname: Shu
authors.forename: Xijuan
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Bingke
authors.initials: B
authors.lastname: Bai
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
authors.forename: Panyong
authors.initials: P
authors.lastname: Mao
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Wang
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015153:Blotting, Western; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D005455:Fluorescent Antibody Technique; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000472:pathogenicity*; D014779:Virus Replication
chemical_list: D018958:CD55 Antigens; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D016899:Interferon-beta
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