title: Susceptibility of naïve and differentiated PC12 cells to Japanese encephalitis virus infection.
abstract: Japanese encephalitis is a mosquito-borne disease caused by Japanese encephalitis virus (JEV) infection. Although JEV infects and replicates in cells with multiple tissue origins, neurons are the preferential cells for JEV infection. Currently, the identities of JEV cell tropism are largely unclear. To gain better insight into the underlying identities of JEV cell tropism, this study was designed to compare the JEV cell tropism with naïve or differentiated PC12 cells. Through nerve growth factor-differentiated PC12 cells, we discovered that JEV efficiently replicated in differentiated PC12 cells rather than naïve cells. Mechanistic studies revealed that viral adsorption/attachment seemed not to be a crucial factor. Supporting data showed that antagonizing postreceptor intracellular signaling of interferons, along with the activation of suppressor of cytokine signaling-3 (SOCS3) expression and protein tyrosine phosphatase activity, were apparent in differentiated PC12 cells after JEV infection. Independent of differentiating inducing agents, the upregulation of SOCS3 expression and protein tyrosine phosphatase activity, as well as preferential JEV tropism, were common in JEV-infected differentiated PC12 cells. Using cultured primary neurons, JEV efficiently replicated in embryonic neurons rather than adult neurons, and the preference was accompanied by higher SOCS3 expression and protein tyrosine phosphatase activity. Given that both SOCS3 and protein tyrosine phosphatases have been implicated in the process of neuronal differentiation, JEV infection seems to not only create an antagonizing strategy to escape host's interferon antiviral response but also takes advantage of cellular machinery to favor its replication. Taken together, current findings imply that dynamic changes within cellular regulators of antiviral machinery could be accompanied by events of neuronal differentiation, thus concurrently playing roles in the control of JEV cell tropism and replication. © 2017 IUBMB Life, 69(2):79-87, 2017.
authors.affiliation: Division of Urology, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Jian-Ri
authors.initials: JR
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Surgery, Feng Yuan Hospital, Taichung City, Taiwan.|Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung City, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Division of Urology, Taichung Veterans General Hospital, Taichung City, Taiwan.|Department of Medical Research, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Yen-Chuan
authors.initials: YC
authors.lastname: Ou
authors.affiliation: Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Division of Family Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung City, Taiwan.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Shue-Ling
authors.initials: SL
authors.lastname: Raung
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung City, Taiwan.
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Liao
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung City, Taiwan.|Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D002454:Cell Differentiation / Q000235:genetics; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000235:genetics / Q000473:pathology / Q000821:virology*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000473:pathology / Q000821:virology; D016716:PC12 Cells; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000096:biosynthesis* / Q000235:genetics; D056189:Viral Tropism / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D017027:Protein Tyrosine Phosphatases
keywords: Flavivirus; cell tropism; innate immunity; interferon; neuronal differentiation