Inherited Irak-4 deficiency in acute human Herpesvirus-6 encephalitis

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buir.contributor.authorTepe, Zeynep Güneş
buir.contributor.authorYazıcı, Yılmaz Yücehan
buir.contributor.authorTank, Umut
buir.contributor.authorKöse, Ladin Işık
buir.contributor.authorBelkaya, Serkan
buir.contributor.orcidTepe, Zeynep Güneş|0000-0002-0575-7737
buir.contributor.orcidTank, Umut|0000-0001-8249-5825
buir.contributor.orcidKöse, Ladin Işık|0000-0002-1449-633X
buir.contributor.orcidBelkaya, Serkan|0000-0003-4214-382X
dc.citation.epage205en_US
dc.citation.spage192en_US
dc.citation.volumeNumber43en_US
dc.contributor.authorTepe, Zeynep Güneş
dc.contributor.authorYazıcı, Yılmaz Yücehan
dc.contributor.authorTank, Umut
dc.contributor.authorKöse, Ladin Işık
dc.contributor.authorÖzer, Murat
dc.contributor.authorAytekin, Caner
dc.contributor.authorBelkaya, Serkan
dc.date.accessioned2023-02-27T21:46:24Z
dc.date.available2023-02-27T21:46:24Z
dc.date.issued2022-10-07
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractHuman herpesvirus-6 (HHV-6) infection can rarely cause life-threatening conditions, such as encephalitis, in otherwise healthy children, with unclear pathogenesis. We studied a child who presented with acute HHV-6 encephalitis at the age of 10 months and who was homozygous for a novel missense mutation in IRAK4, encoding interleukin-1 receptor-associated kinase 4, identified by whole-exome sequencing. We tested the damaging impact of this mutation in silico by molecular dynamics simulations and in vitro by biochemical and functional experiments utilizing cell lines and patient’s cells. We found that the mutation is severely hypomorphic, impairing both the expression and function of IRAK-4. Patient’s leukocytes had barely detectable levels of IRAK-4 and diminished anti-viral immune responses to various stimuli inducing different Toll-like receptors and cytosolic nucleic acid sensors. Overall, these findings suggest that acute HHV-6 encephalitis can result from inborn errors of immunity to virus. This study represents the first report of isolated acute HHV-6 infection causing encephalitis in an inherited primary immunodeficiency, notably autosomal recessive (AR) partial IRAK-4 deficiency, and the first report of AR IRAK-4 deficiency presenting with a severe viral disease, notably HHV-6 encephalitis upon an acute infection, thereby expanding the clinical spectrum of IRAK-4 deficiency.en_US
dc.description.provenanceSubmitted by Zeliha Bucak Çelik (zeliha.celik@bilkent.edu.tr) on 2023-02-27T21:46:24Z No. of bitstreams: 1 Inherited_Irak-4_deficiency_in_acute_human_Herpesvirus-6_encephalitis.pdf: 6603329 bytes, checksum: be73133e6f88d4024f36a3b410c1d24d (MD5)en
dc.description.provenanceMade available in DSpace on 2023-02-27T21:46:24Z (GMT). No. of bitstreams: 1 Inherited_Irak-4_deficiency_in_acute_human_Herpesvirus-6_encephalitis.pdf: 6603329 bytes, checksum: be73133e6f88d4024f36a3b410c1d24d (MD5) Previous issue date: 2022-10-07en
dc.identifier.doi10.1007/s10875-022-01369-4en_US
dc.identifier.issn0271-9142
dc.identifier.issn1573-2592
dc.identifier.urihttp://hdl.handle.net/11693/111861
dc.language.isoEnglishen_US
dc.publisherSpringeren_US
dc.relation.isversionofhttps://doi.org/10.1007/s10875-022-01369-4en_US
dc.source.titleJournal of Clinical Immunologyen_US
dc.titleInherited Irak-4 deficiency in acute human Herpesvirus-6 encephalitisen_US
dc.typeArticleen_US

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