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.
Keywords:
Hearing loss; Human cytomegalovirus; IE2; SLITRK6.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Astrocytes / metabolism*
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Astrocytes / pathology
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Astrocytes / virology
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Cell Line
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Cell Line, Tumor
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Cytomegalovirus / genetics*
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Cytomegalovirus / growth & development
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Cytomegalovirus / pathogenicity
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Fibroblasts / virology
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Gene Expression Regulation
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Hearing Loss, Sensorineural / pathology
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Hearing Loss, Sensorineural / virology
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Host-Pathogen Interactions
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Humans
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Immediate-Early Proteins / genetics*
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Immediate-Early Proteins / metabolism
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Induced Pluripotent Stem Cells / metabolism
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Induced Pluripotent Stem Cells / pathology
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Induced Pluripotent Stem Cells / virology
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Neuroglia / metabolism*
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Neuroglia / pathology
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Neuroglia / virology
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Signal Transduction
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Trans-Activators / genetics*
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Trans-Activators / metabolism
Substances
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IE2 protein, Cytomegalovirus
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Immediate-Early Proteins
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Membrane Proteins
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Slitrk6 protein, human
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Trans-Activators