Detection frequency of human herpesviruses-6A, -6B, and -7 genomic sequences in central nervous system DNA samples from post-mortem individuals with unspecified encephalopathy

Abstract

In this autopsy-based study, human herpesvirus-6 (HHV-6) and -7 (HHV-7) genomic sequence frequency, HHV-6 variants, HHV-6 load and the expression of HHV-6 antigens in brain samples from the individuals, with and without unspecified encephalopathy (controls), using nested and real-time polymerase chain reactions, restriction endonuclease, and immunohistochemical analysis were examined. GraphPad Prism 6.0 Mann-Whitney nonparametric and chi-square test and Fisher's exact test were used for statistical analysis. The encephalopathy diagnoses were shown by magnetic resonance imaging made during their lifetime and macro- and microscopically studied autopsy tissue materials. Widespread HHV-6 and/or HHV-7 positivity was detected in the brain tissue of various individuals with encephalopathy, as well as in controls (51/57, 89.4 % and 35/51, 68.6 %, respectively; p = 0.009). Significantly higher detection frequency of single HHV-6 and concurrent HHV-6 + HHV-7 DNA was found in pia mater meninges, frontal lobe, temporal lobe, and olfactory tract DNAs in individuals with encephalopathy compared to the control group. HHV-6 load and higher frequency of the viral load >10 copies/10(6) cells significantly differed in samples from individuals with and without encephalopathy. The expression of HHV-6 antigens was revealed in different neural cell types with strong predominance in the encephalopathy group. In all HHV-6-positive autopsy samples of individuals with and without encephalopathy, HHV-6B was revealed. Significantly higher detection frequency of beta-herpesvirus DNA, more often detected HHV-6 load >10 copies/10(6) cells, as well as the expression of HHV-6 antigens in different brain tissue samples from individuals with encephalopathy in comparison with control group indicate on potential involvement of these viruses in encephalopathy development.

Evidence of Human Parvovirus B19 Infection in the Post-Mortem Brain Tissue of the Elderly

“…Brain tissue autopsies of 48 individuals were included in the study with the aim to detect B19V DNA, antigens, as well as virions in brain cells. Brain tissue samples from the frontal and temporal cortex, and subcortical white matter selected from 24 elderly people with an unspecified encephalopathy (UEP) (mean age 63.9 (range 42–78); 12 males and 8 females) and 24 age-matched controls (mean age 61.4 (range 49–74); 16 males and 1 female) were used in accordance with the diagnostic criteria for UEP described in a previous study [ 25 ]. UEP-negative controls were chosen using the following inclusion criteria: (1) diagnosis of an encephalopathy was excluded by pathomorphological examination of the brain, applying measurements and calculations of the cerebral ventricle dimensions relative to the skull, as well as by microscopic evidence as described by Chapenko and colleagues [ 25 ]; (2) no prior history of neurological disorders, cerebrovascular disease, as well as traumatic brain injury, and no history of addiction-inducing substance use; and (3) common types of encephalopathy (metabolic, toxic, ischemic, and hemorrhagic) excluded during the lifetime and/or during autopsy.…”

Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

“…The criteria for inclusion in the encephalopathy group were 1) diagnosis of an encephalopathy determined by pathomorphological examination of the brain, applying measurements and calculations of the cerebral ventricle dimensions relative to the skull as well as by microscopic evidence as described by Chapenko and colleagues [32], 2) no prior history of neurological disorders, cerebrovascular disease, as well as traumatic brain injury, and no history of addiction-inducing substance use 3) common types of encephalopathy (metabolic, toxic, ischemic and hemorrhagic) excluded during the lifetime and/or during autopsy. Controls were created using the same inclusion criteria except the pathomorphological changes consistent with encephalopathy, and younger controls were used to exclude age related changes.…”

Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

“…Viral encephalitis frequently involves the meninges, causing meningoencephalitis, or the spinal cord, eliciting encephalomyelitis. Encephalopathy is mediated via metabolic processes and can be caused by systemic infection that spares the brain (Chapenko et al 2016 ; Miranda et al 2011 ; Raspall-Chaure et al 2013 ; Steiner et al 2010 ).…”

“…Human herpesvirus 6 species A and B (HHV-6A and HHV-6B; Ablashi et al 1991 ; Dagna et al 2013 ; Salahuddin et al 2007 ) and HHV-7 (Frenkel et al 1990 ) have been regarded as lymphotropic and neurotropic viruses (Ablashi et al 2000 ; Chapenko et al 2016 ; Savolainen et al 2005 ). In Africa, 86–100% of infants acquire HHV-6A without specific symptoms (Bates et al 2009 ; Hall et al 2006 ; Kasolo et al 1997 ; Sjahril et al 2009 ), but a recent study has shown that in biobanked sera specimens from hospitalized Zambian children between 3 weeks and 2 years of age who were admitted with febrile illness, HHV-6B DNAemia was predominant over HHV-6A (20.5 % versus 0.3 %; Tembo et al 2015 ).…”