Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potenti...

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Main Authors:	Abdelmagid, Nada, Bereczky-Veress, Biborka, Atanur, Santosh, Musilová, Alena, Zídek, Václav, Saba, Laura, Warnecke, Andreas, Khademi, Mohsen, Studahl, Marie, Aurelius, Elisabeth, Hjalmarsson, Anders, Garcia-Diaz, Ana, Denis, Cécile V., Bergström, Tomas, Sköldenberg, Birgit, Kockum, Ingrid, Aitman, Timothy, Hübner, Norbert, Olsson, Tomas, Pravenec, Michal, Diez, Margarita
Format:	Online
Language:	English
Published:	Public Library of Science 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880288/

id	pubmed-4880288
recordtype	oai_dc
spelling	pubmed-48802882016-06-09 Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis Abdelmagid, Nada Bereczky-Veress, Biborka Atanur, Santosh Musilová, Alena Zídek, Václav Saba, Laura Warnecke, Andreas Khademi, Mohsen Studahl, Marie Aurelius, Elisabeth Hjalmarsson, Anders Garcia-Diaz, Ana Denis, Cécile V. Bergström, Tomas Sköldenberg, Birgit Kockum, Ingrid Aitman, Timothy Hübner, Norbert Olsson, Tomas Pravenec, Michal Diez, Margarita Research Article Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines—generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89–174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11–2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE. Public Library of Science 2016-05-25 /pmc/articles/PMC4880288/ /pubmed/27224245 http://dx.doi.org/10.1371/journal.pone.0155832 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Abdelmagid, Nada Bereczky-Veress, Biborka Atanur, Santosh Musilová, Alena Zídek, Václav Saba, Laura Warnecke, Andreas Khademi, Mohsen Studahl, Marie Aurelius, Elisabeth Hjalmarsson, Anders Garcia-Diaz, Ana Denis, Cécile V. Bergström, Tomas Sköldenberg, Birgit Kockum, Ingrid Aitman, Timothy Hübner, Norbert Olsson, Tomas Pravenec, Michal Diez, Margarita
spellingShingle	Abdelmagid, Nada Bereczky-Veress, Biborka Atanur, Santosh Musilová, Alena Zídek, Václav Saba, Laura Warnecke, Andreas Khademi, Mohsen Studahl, Marie Aurelius, Elisabeth Hjalmarsson, Anders Garcia-Diaz, Ana Denis, Cécile V. Bergström, Tomas Sköldenberg, Birgit Kockum, Ingrid Aitman, Timothy Hübner, Norbert Olsson, Tomas Pravenec, Michal Diez, Margarita Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
author_facet	Abdelmagid, Nada Bereczky-Veress, Biborka Atanur, Santosh Musilová, Alena Zídek, Václav Saba, Laura Warnecke, Andreas Khademi, Mohsen Studahl, Marie Aurelius, Elisabeth Hjalmarsson, Anders Garcia-Diaz, Ana Denis, Cécile V. Bergström, Tomas Sköldenberg, Birgit Kockum, Ingrid Aitman, Timothy Hübner, Norbert Olsson, Tomas Pravenec, Michal Diez, Margarita
author_sort	Abdelmagid, Nada
title	Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
title_short	Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
title_full	Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
title_fullStr	Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
title_full_unstemmed	Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
title_sort	von willebrand factor gene variants associate with herpes simplex encephalitis
description	Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines—generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89–174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11–2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
publisher	Public Library of Science
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880288/
_version_	1613584135044988928

Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

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