title: Human cytomegalovirus downregulates SLITRK6 expression through IE2.
abstract: Congenital human cytomegalovirus (HCMV) infection causes sensorineural hearing loss (SNHL) and other neurological disorders, although the neuropathogenesis of HCMV infection is not well understood. Here, we show that the expression of SLITRK6, one of causative genes for hereditary SNHL, was robustly downregulated by HCMV infection in cultured neural cells. We also show that HCMV-encoded immediate-early 2 (IE2) proteins mediate this downregulation and their carboxy-terminal region, especially amino acid residue Gln548, has a critical role. These findings suggest that the downregulation of SLITRK6 expression by IE2 may have a role in HCMV-induced SNHL and other neurological disorders.
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Huanan
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Chiba
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.affiliation: Department of Reproductive Biology, Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. nakamura-hry@ncchd.go.jp.
authors.forename: Hiroyuki
authors.identifier: 0000-0003-0694-2632
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D006319:Hearing Loss, Sensorineural / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; C581991:Slitrk6 protein, human; D015534:Trans-Activators
keywords: Hearing loss; Human cytomegalovirus; IE2; SLITRK6