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. 2020 May 11;10(5):287.
doi: 10.3390/brainsci10050287.

Persistent Roseoloviruses Infection in Adult Patients with Epilepsy

Santa Rasa-Dzelzkaleja  1 , Sabine Gravelsina  1 , Svetlana Chapenko  1 , Zaiga-Nora Krukle  1 , Simons Svirskis  1 , Normunds Suna  2 , Elena Kashuba  3 , Guntis Karelis  2 , Modra Murovska  1
Affiliations

Persistent Roseoloviruses Infection in Adult Patients with Epilepsy

Santa Rasa-Dzelzkaleja et al. Brain Sci. .

Abstract

Background: Human herpesviruses (HHV)-6A, HHV-6B and HHV-7 are considered to be involved in the pathogenesis of epilepsy, a common neurological disorder. The objective of this study was to determine the association of roseoloviruses infection with epilepsy.

Methods: 53 epilepsy patients and 104 ordinary blood donors were analyzed to determine presence of virus-specific antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), genomic sequences, viral load and gene expression by polymerase chain reactions (PCRs) and restriction analysis, HHV-6 protein expression by IFA and level of cytokines by ELISA.

Results: Roseoloviruses genomic sequences in DNA samples from whole blood were found in 86.8% of patients versus 54.8% of controls and active infection was revealed only in patients with epilepsy (19.6% of roseolovirus-positive patients). Significantly higher viral load and more frequent gene expression was detected in patients compared to the controls. HHV-6-encoded protein expression was demonstrated in 53.3% of patients with previously detected HHV-6 DNA. Changes in level of cytokines were determined in patients with elevated viral load compared to the patients without elevated viral loads and to the controls.

Conclusions: Results on frequent active HHV-6 and HHV-7 infection in epilepsy patient' peripheral blood indicate on possible involvement of these viruses in the disease development.

Keywords: epilepsy; human herpesvirus-6; human herpesvirus-7; reactivation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
HHV-6 load in whole peripheral blood (WPB) of the patients with epilepsy (including cases with dual HHV-6 and HHV-7 infection) and control group individuals: (a) Comparison of frequency of HHV-6 positive (pos) and negative (neg) cases in epilepsy patients and control individuals; (b) comparison of viral load and frequency of HHV-6 positive epilepsy patients and control individuals, light symbols indicate cases with double HHV-6 and HHV-7 infection, with red ovals are marked low viral load (<10 copies/106 cells) cases, with green ovals—elevated viral load (>10 copies/106 cells) cases; asterisks in a represent a significance level of differences between groups (*** p < 0.001, **** p < 0.0001).
Figure 2
Figure 2
HHV-7 load in whole peripheral blood (WPB) of the patients with epilepsy (including cases with dual HHV-7 and HHV-6 infection) and control group individuals: (a) comparison of frequency of HHV-7 positive (pos) and negative (neg) cases in epilepsy patients and control individuals; (b) comparison of viral load and frequency of HHV-7 positive epilepsy patients and control individuals, with red ovals are marked low viral load (<10 copies/106 cells) cases, with green ovals—elevated viral load (> 10 copies/106 cells) cases; (c) comparison of elevated viral loads of HHV-7 in epilepsy patients and control individuals; light symbols indicate cases with double HHV-7 and HHV-6 infection (b,c); asterisks in a represent a significance level of differences between groups (** p < 0.01, **** p < 0.0001).
Figure 3
Figure 3
Comparative blood plasma level of TNF-α in epilepsy patients: (a) scatter plots with medians of HHV-6 and HHV-7 negative (neg) and HHV-6 and HHV-7 positive viral load (<10 and >10 copies/106 cells), gray symbols (marked with red ovals) show values below quantification limit (QL); (b) scatter plots with bars (medians with IQR) that represent values above QL (marked with green ovals in a) of HHV-6 and HHV-7 negative (neg) and HHV-6 and HHV-7 positive viral load (<10 and >10 copies/106 cells), values below QL are excluded; asterisks and respective p value represent significance level of differences between the groups (KW—Kruskal–Wallis test).
Figure 4
Figure 4
Comparative blood plasma level of IL-12 in epilepsy patients: (a) scatter plots with medians of HHV-6 and HHV-7 negative (neg) and HHV-6 and HHV-7 positive viral load (<10 and >10 copies/106 cells), gray symbols (marked with red ovals) show values below quantification limit (QL); (b) scatter plots with bars (medians with IQR) that represent values above QL (marked with green ovals in a) of HHV-6 and HHV-7 negative (neg) and HHV-6 and HHV-7 positive viral load (<10 and >10 copies/106 cells), values below QL are excluded; asterisks and respective p represent significance level of differences between the groups (KW—Kruskal–Wallis test).
Figure 5
Figure 5
Comparative blood plasma level of IL-10 in epilepsy patients: (a) scatter plots with medians of HHV-6 and HHV-7 negative (neg) and HHV-6 and HHV-7 positive viral load (<10 and >10 copies/106 cells), gray symbols (marked with red ovals) show values below quantification limit (QL); (b) scatter plots with bars (medians with IQR) that represent values above QL (marked with green ovals in a) of HHV-6 and HHV-7 negative (neg) and HHV-6 and HHV-7 positive viral load (<10 and >10 copies/106 cells), values below QL are excluded; asterisks and respective p represent significance level of differences between the groups (KW—Kruskal–Wallis test).
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