Possible Role of Human Herpesvirus 6 as a Trigger of Autoimmune Disease

Abstract

Human herpesvirus 6 (HHV-6) infection is common and has a worldwide distribution. Recently, HHV-6A and HHV-6B have been reclassified into two distinct species based on different biological features (genetic, antigenic, and cell tropism) and disease associations. A role for HHV-6A/B has been proposed in several autoimmune disorders (AD), including multiple sclerosis (MS), autoimmune connective tissue diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the above-mentioned AD associated with HHV-6 and the mechanisms proposed for HHV-6A/B-induced autoimmunity. HHV-6A/B could trigger autoimmunity by exposing high amounts of normally sequestered cell antigens, through lysis of infected cells. Another potential trigger is represented by molecular mimicry, with the synthesis of viral proteins that resemble cellular molecules, as a mechanism of immune escape. The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of autoantigens. CD46-HHV-6A/B interaction is a new attractive mechanism proposed: HHV-6A/B (especially HHV-6A) could participate in neuroinflammation in the context of MS by promoting inflammatory processes through CD46 binding. Although HHV-6A/B has the ability to trigger all the above-mentioned mechanisms, more studies are required to fully elucidate the possible role of HHV-6A/B as a trigger of AD.

The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance?

“…Among viral infections, EBV shows the strongest association, and it was estimated that EBV-induced infectious mononucleosis increases the risk of MS to a similar degree as the strongest genetic risk factor (HLA-DRB1*15:01) [4,[9][10][11]. In addition to EBV, several other viruses have been implicated in MS [12], in particular neurotropic viruses, including human herpes virus-6 (HHV-6) [13], herpes zoster virus [14] and John Cunningham virus (JCV) [15], but also endogenous retroviruses [16]. Based on this evidence, a possible viral etiology of MS has been proposed [9,13,15,17] and continues to stimulate intense research in the field [ 6 7 1 _ T D $ D I F F ] (see Outstanding Questions).…”

HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis

“…Although originally considered lymphotropic, the in vivo tropism of both viruses is considerably broader, including macrophages, endothelial cells, salivary glands, and brain [5]. HHV-6B is associated with childhood exanthema subitum , whereas HHV-6A is mostly adult-associated, and has been correlated to several chronic autoimmune inflammatory diseases, including AITD [5, 9]. …”

Severe Delayed Drug Reactions

“…111–114 Recent studies have shown an association between AITD and HHV-6 infection and in vitro HHV-6 virus modulation of micro RNA expression in thyrocytes and T-cell lines. 115–118 …”