Human herpesvirus-6 encoded G-protein coupled receptors U12 and U51 and thyroid autoimmunity

Description

Background and aims. Studies have linked HHV-6 with thyroid autoimmunity, yet the exact mechanisms of HHV-6 involvement remain unclear. We propose that two poorly studied HHV-6 proteins – U12 and U51, may contribute to autoimmunity. They are homologous to chemokine receptors (G-protein coupled receptors), can be expressed on cell surfaces, and can influence viral replication. By conducting molecular and immunological investigations we aim to elucidate the potential role of U12/U51 in thyroid autoimmunity.
Methods. Thyroid tissue and plasma samples from 81 AIT patients (harboring HHV-6 in the thyroid) were investigated. RNA was isolated from thyroid tissues, used for cDNA synthesis, and nPCR to detect U12, U51 mRNA. FFPE thyroid tissues were microscoped to visualize U12/U51. U12 and U51 antibodies were detected with the Luminex system.
Results. 46% of thyroid tissue samples harbored U12/U51 mRNA. Thyroid tissues with mRNA harbored significantly higher viral loads (1390 vs 120 viral copies/106 cells, p = 0.01). Nearly all AIT patients had U12/U51 antibodies, and in those with active HHV-6 infection, antibody levels were significantly higher. Microscopy revealed the colocalization of HHV-6 and U12/U51 in the thyroid.
Conclusions. The combination of the presence of U12/U51 mRNA and viral protein-specific antibodies with the visualization of both HHV-6 and its GPCRs in the thyroid suggests that both could be involved in autoimmunity development/exacerbation. HHV-6 and U12/U51 could enhance thyroid cell destruction, autoantigen release, and inflammation through viral replication enhancement or through direct antibody binding and subsequent immune response against U12/U51.
Acknowledgments: EU Horizon 2020 project “Reducing networking gaps between RSU and internationally leading counterparts in viral infection-induced autoimmunity research (VirA)” (No. 952376)

Period	16 Feb 2024
Event title	Viruses 2024 - A World of Viruses
Event type	Conference
Location	Barcelona, SpainShow on map
Degree of Recognition	International