Fig. 1

Potential mechanism of muscle fatigue is related to acute immunosuppressive and chronic inflammatory mechanisms of HHV6 viral infection. Acute infection of HHV6 (Blue shade) causes immunosuppression. During that phase, virus-infected CD4 + Th1 and CD8 + Tc cells undergo apoptosis (#1) following phagocytosis (#2) by macrophages (Mφ). During phagocytosis, Mφ release TGFβ and IL10 as a part of the immune tolerance response (#3). IL10 and IL4 are also secreted from Th2 cells during activation of FOXP3^+ve regulatory T cells. Together, there is an immunosuppressive response marked with reduction of inflammatory cytokines (#4). However, during chronic inflammation and viral reactivation (Red shade), a subset of persistently infected Th1 cells escape apoptosis, undergo clonal proliferation (IL2 and IL12) (#1), engage in crosstalk with Mφ, build up inflammatory milieu (#2), generate oxidatively (ROS = reactive oxygen species) and nitrosative stress (NO = nitric oxide) (#3). These inflammatory T cells also infiltrate through the blood–brain barrier (BBB), interacts with microglia causing CNS inflammation, demyelination of oligos, demyelination of nerve fibers (#4), and finally leads to the impaired nerve conduction, muscle weakness, and fatigue. FOXP3 = forkhead box P3; A master transcription factor in the development and function of regulatory T cells