Possible involvement of human herpesvirus-6 U12 and U51 gene coded proteins in the development of autoimmunity – an immunological investigation

Activity: Talk or presentation typesOral presentation

Description

Objectives

HHV-6 has frequently been detected in autoimmune thyroiditis tissues, possibly implicating the infection in the
initiation of autoimmunity. We investigated the role of two virally encoded chemokine receptor homologues
(U12 and U51) as autoimmunity triggers by using potentially immunogenic peptides designed from viral protein
amino acid sequences.

Materials and Methods

Blood plasma from 64 autoimmune thyroiditis patients was analyzed in this study. Prior to this study thyroid
tissues from these patients were analyzed for HHV-6 presence, and all were demonstrated to harbor HHV-6
genomic sequences.
U12 and U51 protein amino acid sequences were aligned with human CCR1, 3 and 5 using the T-Coffee software.
Alignment was combined with linear epitope prediction algorithms to design 20 mer peptides. Acquired viral
peptides and recombinant human CCR1, 3 and 5 were conjugated to magnetic beads. Blood plasma and the conjugated
beads were used in Suspension Multiplex Immunological Assay for the detection of human chemokine
receptor and viral peptide specific IgG and IgM antibodies and the evaluation of peptide specific antibody crossreactivity.

Results

Antibodies specific for several viral peptides were found in patient plasma samples. Peptides with highest MFI
values were selected for cross-reactivity assessment. Overall MFI values for peptide specific IgM antibodies
were significantly higher compared to IgG antibodies. Interestingly, patient plasma contained antibodies for
two of the human chemokine receptors - CCR1 and 5. Again, MFI values for receptor specific IgM antibodies
were much higher. Eluted peptide specific antibodies were not able to bind human chemokine receptors – no
cross-reactivity was observed.

Conclusions

HHV-6 peptide specific antibodies were found in patient’s samples, with higher signals for IgM antibodies, indicating
HHV-6 reactivation and active infection. Even though, no cross reactivity between HHV-6 peptide specific
antibodies and human recombinant CCR1, 3 and 5 was found, further investigation of potential conformational
epitopes is necessary.
Period24 Mar 2021
Event titleRSU Research week 2021: Knowledge for Use in Practice
Event typeConference
LocationRīga, Latvia
Degree of RecognitionInternational