Differentiated human neural stem cells: a new ex vivo model to study HHV-6 infection of the central nervous system.
BACKGROUND
HHV-6 is the etiologic agent of exanthem subitum, a pediatric illness that may be associated with clinical and laboratory signs of central nervous system involvement. The absence of suitable experimental models has so far hampered the elucidation of the mechanisms of HHV-6-mediated neural cell damage. Recently, the growing knowledge in neurobiology has permitted the establishment of long-term cultures of human neural stem cells (hNSC) that, by virtue of their self-renewal capacity and multipotentiality, provide a valuable tool for the study of neurodegenerative disorders.


OBJECTIVE
We studied the effects of HHV-6 infection in differentiated cultures of hNSC derived from the telencephalic and diencephalic regions of a 13.5 week post conception (pcw) fetal brain. The prototypic HHV-6 strain GS (subgroup A) was used.


RESULTS
hNSC were differentiated ex vivo to obtain mixed cultures encompassing astrocytes, neurons and oligodendrocytes. These differentiated hNSC cultures were found to be susceptible to productive HHV-6A infection, resulting in the formation of syncytia associated with phenotypic alterations.


CONCLUSIONS
These results demonstrate that hNSC may provide a physiologically relevant model to investigate the pathogenic role of HHV-6 in central nervous system disorders.
De Filippis
Lidia
L
Stem Cell Research Institute, DIBIT, San Raffaele Scientific Institute 20132 Milan, Milan, Italy.
Foglieni
Chiara
C
Silva
Sara
S
Vescovi
Angelo L
AL
Lusso
Paolo
P
Malnati
Mauro S
MS
D001253:Astrocytes / Q000821:virology*; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D020805:Central Nervous System Viral Diseases / Q000821:virology; D015726:Giant Cells / Q000166:cytology; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000821:virology*; D009836:Oligodendroglia / Q000821:virology*; D019349:Roseolovirus Infections / Q000821:virology; D013234:Stem Cells / Q000821:virology*