Infection of human oligodendroglioma cells by a recombinant measles virus expressing enhanced green fluorescent protein

Abstract

One of the hallmarks of the human CNS disease subacute sclerosing panencephalitis (SSPE) is a high level of measles virus (MV) infection of oligodendrocytes. It is therefore surprising that there is only one previous report of MV infection of rat oligodendrocytes in culture and no reports of human oligodendrocyte infection in culture. In an attempt to develop a model system to study MV infection of oligodendrocytes, time-lapse confocal microscopy, immunocytochemistry, and electron microscopy (EM) were used to study infection of the human oligodendroglioma cell line, MO3.13. A rat oligodendrocyte cell line, OLN-93, was also studied as a control. MO3.13 cells were shown to be highly susceptible to MV infection and virus budding was observed from the surface of infected MO3.13 cells by EM. Analysis of the infection in real time and by immunocytochemistry revealed that virus spread occurred by cell-to-cell fusion and was also facilitated by virus transport in cell processes. MO3.13 cells were shown to express CD46, a MV receptor, but were negative for the recently discovered MV receptor, signaling leucocyte activation molecule (SLAM). Immunohistochemical studies on SSPE tissue sections demonstrated that CD46 was also expressed on populations of human oligodendrocytes. SLAM expression was not detected on oligodendrocytes. These studies, which are the first to show MV infection of human oligodendrocytes in culture, show that the cells are highly susceptible to MV infection and this model cell line has been used to further our understanding of MV spread in the CNS.

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

“…It should be noted that signaling lymphocyte-activation molecule (SLAM) is considered the main receptor for some wild-type strains of MV, while CD46 is used preferentially by vaccine strains and certain other wildtype strains (Schneider-Schaulies et al, 1995). However, because SLAM is not expressed by brain cells (McQuaid and Cosby, 2002;Plumb et al, 2002) other mechanisms are responsible for MV spread in the CNS. It has been shown that a single amino acid substitution in the sequence of HA (from asparagine or lysine to tyrosine in position 481) allows wild-type strains of MV to interact with CD46, while preserving the ability to bind SLAM (Buckland and Wild, 1997).…”

Vesicular Stomatitis Virus as an Oncolytic Vector

“…These include reovirus as well as members of the Paramyxovirus and Orthomyxovirus families, consisting of measles virus, Newcastle disease virus, mumps and influenza viruses (28,33,35,36,38,48,57,66,70,76,78,80,95). Even Picornaviruses, such as poliovirus, have been demonstrated to exert oncolytic effects, as well as cytolytic replicating RNAs derived from alphaviruses (3,32,94,95).…”

Approaches in the Understanding of Morbillivirus Neurovirulence

“…In addition to neurones, MV antigen ( Figure 1A) and RNA is present in oligodendrocytes and, to a lesser degree, in astrocytes and endothelial cells in SSPE brain (Kirk et al, 1991;Plumb et al, 2002). Viral RNA and antigen are also present in inflammatory cells in perivascular cuffs (Cosby et al, 1989;Allen et al, 1996).…”