title: Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection.
abstract: 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.
authors.affiliation: Institute of Anatomy and Anthropology, Riga Stradins University, Riga, Latvia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Skuja
authors.affiliation: Institute of Anatomy and Anthropology, Riga Stradins University, Riga, Latvia.
authors.forename: Anete
authors.initials: A
authors.lastname: Zieda
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Kristine
authors.initials: K
authors.lastname: Ravina
authors.affiliation: A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Chapenko
authors.affiliation: Department of Pathology, Riga 1st Hospital, Riga, Latvia.
authors.forename: Silvija
authors.initials: S
authors.lastname: Roga
authors.affiliation: Latvian State Centre for Forensic Medical Examination, Riga, Latvia.
authors.forename: Ojars
authors.initials: O
authors.lastname: Teteris
authors.affiliation: Institute of Anatomy and Anthropology, Riga Stradins University, Riga, Latvia.
authors.forename: Valerija
authors.initials: V
authors.lastname: Groma
authors.affiliation: A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia.
authors.forename: Modra
authors.initials: M
authors.lastname: Murovska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D017628:Microglia / Q000648:ultrastructure / Q000821:virology; D008875:Middle Aged; D009474:Neurons / Q000648:ultrastructure / Q000821:virology; D009830:Olfactory Bulb / Q000473:pathology* / Q000821:virology; D019349:Roseolovirus Infections / Q000150:complications / Q000473:pathology* / Q000821:virology