PMID- 28072884 OWN - NLM STAT- MEDLINE DCOM- 20170811 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 1 DP - 2017 TI - Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection. PG - e0170071 LID - 10.1371/journal.pone.0170071 [doi] LID - e0170071 AB - Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them. FAU - Skuja, Sandra AU - Skuja S AD - Institute of Anatomy and Anthropology, Riga Stradins University, Riga, Latvia. FAU - Zieda, Anete AU - Zieda A AD - Institute of Anatomy and Anthropology, Riga Stradins University, Riga, Latvia. FAU - Ravina, Kristine AU - Ravina K AD - Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Chapenko, Svetlana AU - Chapenko S AD - A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia. FAU - Roga, Silvija AU - Roga S AD - Department of Pathology, Riga 1st Hospital, Riga, Latvia. FAU - Teteris, Ojars AU - Teteris O AD - Latvian State Centre for Forensic Medical Examination, Riga, Latvia. FAU - Groma, Valerija AU - Groma V AD - Institute of Anatomy and Anthropology, Riga Stradins University, Riga, Latvia. FAU - Murovska, Modra AU - Murovska M AD - A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia. LA - eng PT - Journal Article DEP - 20170110 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Adolescent MH - Adult MH - Aged MH - Brain Diseases/etiology/*pathology/virology MH - Case-Control Studies MH - Female MH - Herpesvirus 6, Human/genetics/isolation & purification MH - Humans MH - Male MH - Microglia/ultrastructure/virology MH - Middle Aged MH - Neurons/ultrastructure/virology MH - Olfactory Bulb/*pathology/virology MH - Roseolovirus Infections/complications/*pathology/virology PMC - PMC5224992 COIS- The authors have declared that no competing interests exist. EDAT- 2017/01/11 06:00 MHDA- 2017/08/12 06:00 PMCR- 2017/01/10 CRDT- 2017/01/11 06:00 PHST- 2016/07/10 00:00 [received] PHST- 2016/12/28 00:00 [accepted] PHST- 2017/01/11 06:00 [entrez] PHST- 2017/01/11 06:00 [pubmed] PHST- 2017/08/12 06:00 [medline] PHST- 2017/01/10 00:00 [pmc-release] AID - PONE-D-16-27503 [pii] AID - 10.1371/journal.pone.0170071 [doi] PST - epublish SO - PLoS One. 2017 Jan 10;12(1):e0170071. doi: 10.1371/journal.pone.0170071. eCollection 2017.