Human Herpesvirus 6 (HHV-6) is a set of two closely related herpes viruses known as HHV-6A and HHV-6B. Both are lymphotropic viruses that establish latency in the host. The ability to evade the immune responses of effector cells is likely a major factor contributing to the development of a persistent HHV-6A/B (collectively termed HHV-6) infection. Natural killer (NK) cells are lymphocytes that, along with neutrophils and monocytes/macrophages, participate in the critical innate immune response during viral infections, but can also mediate the antigen-specific memory responses generally associated with adaptive immunity. NK cells compose the first barrier that viruses must break through to continue replication and dissemination, and a weak NK cell response may predispose an individual to chronic viral infections. Both HHV-6A and HHV-6B can interfere with NK cell-mediated anti-viral responses but the mechanisms by which each of these viruses affect NK cell activity differs. In this review, we will explore the nuanced relationships between the two viruses and NK cells, discussing, in addition, relevant disease associations.
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