CD46 on glial cells can function as a receptor for viral glycoprotein‐mediated cell–cell fusion

Abstract

Membrane cofactor protein (CD46) is a regulator of complement activation that also serves as the entry receptor for human herpes virus 6 (HHV-6) and measles virus (MV) into human cells. While it is clear that oligodendrocytes and astrocytes are cell types commonly infected by these viruses, it is unclear whether oligodendrocytes express CD46, or which are the cellular mechanisms underlying the infection. We show that adult oligodendrocytes, as well as astrocytes and microglial cells, express CD46 on the cellular surface. Moreover, we employed a quantitative fusion assay to demonstrate that HHV-6A infection of T lymphocytes enables cell-cell fusion of these cells to astrocytes or to oligodendroglial cells. This fusion is mediated by the interaction between viral glycoproteins expressed on the membrane of the infected cells and CD46 on the glial targets, and is also observed using cells expressing recombinant MV glycoproteins. These data suggest a mechanism that involves cell-cell fusion by which certain viruses could spread the infection from the periphery to the cells in the nervous system.

Human herpesvirus-6 entry into the central nervous system through the olfactory pathway

“…One proposed site of HHV-6 latency is in the tonsils and adenoids, where the virus has been shown to be actively shed in saliva (15,16). In addition, many in vitro studies have demonstrated that HHV-6 has a tropism for glial cells that may also represent an in vivo reservoir of viral latency in the CNS (17)(18)(19)(20). Although HHV-6 is increasingly recognized as an important pathogen in a number of neurologic diseases, how the virus gains access to the CNS is not completely understood.…”

U20 Is Responsible for Human Herpesvirus 6B Inhibition of Tumor Necrosis Factor Receptor-Dependent Signaling and Apoptosis

“…Productive HHV-6B infection occurs primarily in CD4 ϩ T cells but may also occur in CD8 ϩ T cells and B cells, although only to a mild extent in the latter case (26). Little is known about the effects of HHV-6B in nonproductively infected cells, but cytoplasmic transport from cell to cell is possible, circumventing tissue barriers (3).…”

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

“…Вновь продуцированные вирионы HSV1 мигрируют в струк-туры лимбической системы -гипоталамус, гиппокамп и миндалину [1,3], поэтому при HSV энцефалите наибольшие повреждения выявляют в лимбической системе [4]. Обонятельный тракт также являет путем проникновения в ЦНС герпеса 6 типа (HHV6) [5,6]. По данным патологоанатомического исследования, в 41% наблюдений в обонятельной луковице обнаружен HHV6 [5,6]; у 18% больных при мезиальной височной эпилепсии (MTLE синдром) в гиппокампе обнаружены вирусы HSV1, HHV6 и HHV8.…”

“…Обонятельный тракт также являет путем проникновения в ЦНС герпеса 6 типа (HHV6) [5,6]. По данным патологоанатомического исследования, в 41% наблюдений в обонятельной луковице обнаружен HHV6 [5,6]; у 18% больных при мезиальной височной эпилепсии (MTLE синдром) в гиппокампе обнаружены вирусы HSV1, HHV6 и HHV8.…”