Figure 2: Potential mechanisms for HHV-6-induced neuroinflammation. (a) Based on similarities between viral proteins and brain proteins, HHV-6A or -6B infection in the periphery could lead to the activation of cross-reactive T and B cells, able to recognize both viral antigens and brain antigens, and to the development of an autoimmune response directed to the brain (molecular mimicry). This would promote lymphocyte infiltration in the CNS, where they could have cytotoxic activities against resident cells, especially oligodendrocytes which express myelin antigens (1). Peripheral infection could also increase the inflammation by inducing IL-17 and inhibiting IL-10 production by T cells through CD46 binding (2). (b) Infection of astrocytes in the brain can lead to the release of proinflammatory cytokines and chemokines, which promote the infiltration of leukocytes expressing the corresponding chemokine receptor (3). Productive infection of CNS cells can result in the production of the viral chemokine U83, which can also attract leukocytes to the brain (4). Finally, infection of endothelial cells can induce the secretion of chemokines, thus attracting circulating leukocytes and facilitating their transmigration through the blood-brain barrier (5).