The Interplay between Natural Killer Cells and Human Herpesvirus-6

Abstract

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.

Unexpected High Incidence of Human Herpesvirus-6 Encephalitis after Naive T Cell–Depleted Graft of Haploidentical Stem Cell Transplantation in Pediatric Patients

“…The interaction between HHV-6 and the immune system is not well known; however, 2 major issues have been already proposed. First, upon infection, NK cells act to control the dissemination of the HHV-6, lysing autologous HHV-6Àinfected peripheral blood mononuclear cells [50]. Second, CD4 + T cells co-expressing CD134 (OX40) contain significantly greater numbers of HHV-6B copies than CD4 + T cells without CD134 expression [51].…”

DNA Sensors’ Signaling in NK Cells During HHV-6A, HHV-6B and HHV-7 Infection

“…HHV-6, as HHV-6A and HHV-6B are commonly called when they are not separated into two species, has a wide cell tropism inducing a lifelong latent infection in humans (Ablashi et al, 2014;Eliassen et al, 2017). HHV-6A/B replicate preferentially in CD4+ T lymphocytes and utilize distinct cell surface receptors: HHV-6A uses CD46, a regulator of complement activation expressed on all nucleated cells, while HHV-6B uses CD134 (also called OX40), a member of the tumor necrosis factor (TNF) receptor superfamily.…”

Human herpesvirus 6A and 6B and NK cells

“…HHV-6A and -6B have a preferential tropism for lymphoid cells (T cells, monocytes/macrophages) but in vitro and in vivo, they can also infect other cell types (endothelial cells, fibroblasts, NK cells, glial cells, astrocytes, hepatocytes, etc.) [8], with different cell target and/or efficiency of infection for the two viral species. In fact, the two viruses use different cell receptors to recognize and attach to the cell membrane.…”