HHV-6 infection can result in the following mechanisms associated with immune suppression/autoimmunity:
- HHV-6 infection is associated with transient hypogammaglobulinemia (Kano 2004).
- Depletion of CD4+ T lymphocytes via direct infection and induction of apoptosis (Grivel 2003, Lusso 1988).
- Lytic infection of cytotoxic effector cells – CD8+, NK cells (Lusso 1991A, Lusso 1995).
- Functional impairment and delay in maturation of dendritic cells and macrophages (Kakimoto 2002, Smith 2005).
- Suppression of the ability of macrophages and dendritic cells to produce IL-12p70 upon stimulation with interferon gamma (Smith 2003, 2005).
- Suppression of IL-2 secretion (Flamand 1995).
- Disturbance of key immune activation pathways and cytokine networks, including an upregulation of TNF-alpha, RANTES, IL-1beta and IL-10 (Flamand 1991, Arena 1999, Grivel 2000).
- Downregulation of complement activity through the CD46 receptor and downregulation of IL-2 (Russell 2004).
- Modification of monocytes that favor immune evasion, including reduced levels of CD14, CD64 and HLA-DR antigen on their surface while CD32 expression is unaffected (Janelle 2006).
- Dysregulation of monocyte-mediated antifungal defenses (Cermelli 2006).
- HHV-6 specific IL-10 producing CD4+ T cells and CD4+ Th1 responses in HHV-6 infected individuals are selectively impaired (Wang 2006).
- Generalized loss of CD46 expression in lymphoid tissue (Lusso 2006).
- Delayed immune response after acute HHV-6 infection (Kumagai 2006).
- Downmodulation of the CD3/T-cell receptor complex (Lusso 1991, Sullivan 2008).
- Suppression of IFN-beta gene induction by IE proteins from HHV-6, interfering with innate antiviral response (Jaworska 2007).
- In a 2012 study, 30% of children with transient neutropenia were found to have an associated HHV-6 infection (Husain 2012).
HHV-6 in Autoimmunity
A role for HHV-6 has been proposed in several autoimmune disorders, including autoimmune hemolytic anemia/neutropenia (Yagasaki 2010), autoimmune acute hepatitis (Grima 2008), and multiple sclerosis (Tejada-Simon 2003, many), among others. A 2012 study has linked HHV-6A to Hashimoto’s thyroiditis (HT), a common autoimmune thyroid disease (AITD) (Caselli 2012). The study found that HHV-6 was detected significantly more frequently among thyroid fine needle aspirates (FNA) from HT individuals than controls (82% vs. 10%, respectively), and low-grade acute infection was identified in all HHV-6 positive HT samples compared to 0% of controls. In addition, the group demonstrated that thyroid cells infected with both HHV-6A and HHV-6B became susceptible to NK-mediated killing, providing evidence of a potential mechanism for HHV-6-induced autoimmunity.