title: Later passages of neural progenitor cells from neonatal brain are more permissive for human cytomegalovirus infection.
abstract: Congenital human cytomegalovirus (HCMV) infection is the most frequent infectious cause of birth defects, primarily neurological disorders. Neural progenitor/stem cells (NPCs) are the major cell type in the subventricular zone and are susceptible to HCMV infection. In culture, the differentiation status of NPCs may change with passage, which in turn may alter susceptibility to virus infection. Previously, only early-passage (i.e., prior to passage 9) NPCs were studied and shown to be permissive to HCMV infection. In this study, NPC cultures derived at different gestational ages were evaluated after short (passages 3 to 6) and extended (passages 11 to 20) in vitro passages for biological and virological parameters (i.e., cell morphology, expression of NPC markers and HCMV receptors, viral entry efficiency, viral gene expression, virus-induced cytopathic effect, and release of infectious progeny). These parameters were not significantly influenced by the gestational age of the source tissues. However, extended-passage cultures showed evidence of initiation of differentiation, increased viral entry, and more efficient production of infectious progeny. These results confirm that NPCs are fully permissive for HCMV infection and that extended-passage NPCs initiate differentiation and are more permissive for HCMV infection. Later-passage NPCs being differentiated and more permissive for HCMV infection suggest that HCMV infection in fetal brain may cause more neural cell loss and give rise to severe neurological disabilities with advancing brain development.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Pan
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Xi-Juan
authors.initials: XJ
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.forename: Jia-Fu
authors.initials: JF
authors.lastname: Li
authors.forename: Ying-Liang
authors.initials: YL
authors.lastname: Duan
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Ye
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Fu
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Qiao
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Tian
authors.forename: Kang-Hong
authors.initials: KH
authors.lastname: Hu
authors.forename: Ling-Feng
authors.initials: LF
authors.lastname: Miao
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zheng
authors.forename: Simon
authors.initials: S
authors.lastname: Rayner
authors.forename: Philip H
authors.initials: PH
authors.lastname: Schwartz
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
authors.forename: Jiang
authors.initials: J
authors.lastname: Xu
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Luo
mesh_terms: D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D003587:Cytomegalovirus / Q000254:growth & development*; D006801:Humans; D058953:Neural Stem Cells / Q000502:physiology* / Q000821:virology*; D012692:Serial Passage
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