title: Pluripotent stem cells are protected from cytomegalovirus infection at multiple points: implications of a new pathogenesis for congenital anomaly caused by cytomegalovirus.
abstract: In humans, the cytomegalovirus (CMV) is the most significant cause of intrauterine infections that cause congenital anomalies. Intrauterine infection with human CMV is thought to be responsible for a variety of abnormalities, including mental retardation, microcephaly, developmental delay, seizure disorders, and cerebral palsy, depending on the timing of the fetal infection, the infectious route, and the virulence of the virus. In addition to the adaptive immune system, the embryo has potential resistance to CMV during early embryogenesis. Embryonic stem (ES) cells are more resistant to CMV than most other cell types, although the mechanism responsible for this resistance is not well understood. ES cells allow approximately 20-fold less murine CMV (MCMV) DNA to enter the nucleus than mouse embryonic fibroblasts (MEFs), and this inhibition occurs in a multistep manner. In situ hybridization showed that ES cell nuclei had significantly less MCMV DNA than MEF nuclei. This finding appears to be supported by the fact that ES cells express less heparan sulfate, β1-integrin, and vimentin and have fewer nuclear pores than differentiated cells such as MEF. This may reduce the ability of MCMV to attach to and enter the cellular membrane, translocate to the nucleus, and cross the nuclear membrane in pluripotent stem cells (ES-induced pluripotent stem cells). This finding may indicate a new pathogenesis for the congenital anomaly caused by CMV.
authors.affiliation: Department of Regenerative & Infectious Pathology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan. gloria@hama-med.ac.jp
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000013:Congenital Abnormalities / Q000209:etiology / Q000821:virology*; D003587:Cytomegalovirus / Q000235:genetics / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000821:virology*; D053595:Embryonic Stem Cells / Q000473:pathology / Q000821:virology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016679:Genome, Viral; D006801:Humans; D051379:Mice; D018146:Muromegalovirus / Q000235:genetics / Q000472:pathogenicity; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*