Susceptibility of human tonsillar epithelial cells to enterovirus 71 with normal cytokine response.
A recent histopathologic study implicated human tonsillar crypt epithelium as an important site for EV71 replication in EV71-caused fatal cases. This study aimed to confirm the susceptibility of human tonsillar epithelium to EV71. Two human tonsillar epithelial cell lines (UT-SCC-60A and UT-SCC-60B) were susceptive to EV71, and PI3K/AKT, p38, ERK1/2, and JNK1/2 signal pathways were activated. Interferon-α, IL-8, IL-1β, IL-6 and IL-12p40 were induced and regulated by PI3K/AKT, p38, ERK1/2, and JNK1/2 signal pathways. PI3K/AKT pathway activation appeared to suppress the induction of TNF-α, which induced cell survival by inhibiting GSK-3β. The activation of NF-κB was observed but inhibited by these pathways in EV71 infection. Furthermore, ERK1/2 and JNK1/2 were essential for efficient EV71 replication. Human tonsillar epithelial cells support EV71 replication and display innate antiviral immunity in vitro, indicating that human tonsillar epithelial cells may be novel targets for EV71 infection and replication in vivo.
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Guang-Cheng
GC
Xie
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Hunan Provincial People's Hospital, the First affiliated Hospital of Hunan Normal University, Changsha, China.
Ni-Jun
NJ
Guo
Department of Otorhinolaryngology-Head and Neck Surgery, Turku University and Turku University Hospital, Turku, Finland.
Reidar
R
Grénman
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Hong
H
Wang
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, China.
Ying
Y
Wang
Department of Otorhinolaryngology-Head and Neck Surgery, Turku University and Turku University Hospital, Turku, Finland.
Minna
M
Vuorenmma
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Qing
Q
Zhang
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Shuang
S
Zhang
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Hui-Ying
HY
Li
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Li-Li
LL
Pang
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Dan-Di
DD
Li
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Miao
M
Jin
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Xiao-Man
XM
Sun
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Xiang-Yu
XY
Kong
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address: zhaojund@126.com.
Zhao-Jun
ZJ
Duan
D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003588:Cytopathogenic Effect, Viral; D004198:Disease Susceptibility; D029821:Enterovirus A, Human / Q000502:physiology*; D004769:Enterovirus Infections / Q000378:metabolism* / Q000821:virology*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D014066:Palatine Tonsil / Q000378:metabolism* / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012367:RNA, Viral; D051116:Receptors, Scavenger / Q000378:metabolism; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C084882:P-selectin ligand protein; D012367:RNA, Viral; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D014764:Viral Proteins; D007633:Keratins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
Cytokine response; EV71; Human tonsillar epithelial cells; MAPKs; PI3K/AKT