Mouse embryonic stem cells are not susceptible to cytomegalovirus but acquire susceptibility during differentiation.
BACKGROUND
Cytomegalovirus (CMV) is the most significant infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection in humans. The timing of infection and the susceptibility of cells in early gestational stages are not well understood. In this study we investigated the susceptibility of embryonic stem (ES) cells to CMV infection during differentiation.


METHODS
ES cell lines were established from transgenic mice integrated with the murine CMV (MCMV) immediate-early (IE) promoter connected with a reporter lacZ gene. The susceptibility of the ES cells was analyzed in terms of viral gene expression and viral replication after induction of differentiation.


RESULTS
ES cells were nonpermissive to MCMV infection in the undifferentiated state. Upon differentiation, permissive cells appeared approximately 2 weeks after the leukemia inhibitory factor was removed. Upon neural differentiation by retinoic acid (RA), glial cells showed specific susceptibility in terms of expression of the viral antigen. The MCMV IE promoter was not activated in ES cells from the transgenic mice. Activation of the IE promoter was detected approximately 2 weeks after induction of differentiation and observed predominantly in glial cells. Upon MCMV infection of the ES cells, viral infection was correlated with the activation of the IE promoter.


CONCLUSIONS
ES cells are nonpermissive to MCMV infection and acquire permissiveness about 2 weeks after induction of differentiation, especially in glial cells. Acquisition of permissiveness in differentiated ES cells may be associated with activation of the IE promoter.
Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Shoichi
S
Matsukage
Isao
I
Kosugi
Hideya
H
Kawasaski
Katsutoshi
K
Miura
Hiroshi
H
Kitani
Yoshihiro
Y
Tsutsui
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004198:Disease Susceptibility; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000473:pathology / Q000821:virology*; D005260:Female; D006566:Herpesviridae Infections / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000472:pathogenicity*; D009457:Neuroglia / Q000166:cytology / Q000473:pathology / Q000821:virology; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000821:virology; D013724:Teratoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013997:Time Factors