Human Induced Pluripotent Stem Cell-Derived Models to Investigate Human Cytomegalovirus Infection in Neural Cells

Leonardo D'Aiuto, Roberto Di Maio, Brianna Heath, Giorgio Raimondi, Jadranka Milosevic, Annie M. Watson, Mikhil Bamne, W. Tony Parks, Lei Yang, Bo Lin, Toshio Miki, Jocelyn Danielle Mich-Basso, Ravit Arav-Boger, Etienne Sibille, Sarven Sabunciyan, Robert Yolken, Vishwajit Nimgaonkar

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Abstract

Human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS) cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs), neural progenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate.

Original languageEnglish (US)
Article numbere49700
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 27 2012

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

D'Aiuto, L., Di Maio, R., Heath, B., Raimondi, G., Milosevic, J., Watson, A. M., Bamne, M., Parks, W. T., Yang, L., Lin, B., Miki, T., Mich-Basso, J. D., Arav-Boger, R., Sibille, E., Sabunciyan, S., Yolken, R., & Nimgaonkar, V. (2012). Human Induced Pluripotent Stem Cell-Derived Models to Investigate Human Cytomegalovirus Infection in Neural Cells. PloS one, 7(11), [e49700]. https://doi.org/10.1371/journal.pone.0049700