2013
DOI: 10.1186/2042-4280-4-2
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Human cytomegalovirus induces apoptosis in neural stem/progenitor cells derived from induced pluripotent stem cells by generating mitochondrial dysfunction and endoplasmic reticulum stress

Abstract: BackgroundCongenital human cytomegalovirus (HCMV) infection, a leading cause of birth defects, is most often manifested as neurological disorders. The pathogenesis of HCMV-induced neurological disorders is, however, largely unresolved, primarily because of limited availability of model systems to analyze the effects of HCMV infection on neural cells.MethodsAn induced pluripotent stem cell (iPSC) line was established from the human fibroblast line MRC5 by introducing the Yamanaka’s four factors and then induced… Show more

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Cited by 31 publications
(34 citation statements)
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“…Fortunately, large populations of almost pure cell types can be generated using either embryonic stem (ES) cell or induced pluripotent stem cell (iPSC) technologies. Interestingly, NPCs derived from 10-week gestation tissue were substantially more permissive to infection (30) than either ES-or iPS-derived NPCs (31)(32)(33)(34)(35)(36)(37)(38); also our unpublished results). This suggests that the more primitive stage of development of the ES-and iPS-derived cells influences their interactions with the virus.…”
mentioning
confidence: 52%
“…Fortunately, large populations of almost pure cell types can be generated using either embryonic stem (ES) cell or induced pluripotent stem cell (iPSC) technologies. Interestingly, NPCs derived from 10-week gestation tissue were substantially more permissive to infection (30) than either ES-or iPS-derived NPCs (31)(32)(33)(34)(35)(36)(37)(38); also our unpublished results). This suggests that the more primitive stage of development of the ES-and iPS-derived cells influences their interactions with the virus.…”
mentioning
confidence: 52%
“…The link between ER stress and NOD1/NOD2 signaling may also be of relevance for other pathologies in which NOD1 and or NOD2 have been implicated in the inflammatory response, such as infection with HCMV infection, which is known to modulate the function of the endoplasmic reticulum for its replication, and induces the unfolded protein response (UPR) [72]. Similarly, the role of NOD2 in sensing influenza virus infection (discussed above) could be related to activation of IRE1α-induced inflammatory responses [71], because influenza virus is known to trigger ER stress [73].…”
Section: Nod1/2 Sensing Of Endoplasmic Reticulum (Er) Stressmentioning
confidence: 99%
“…Recientemente, se ha estudiado el efecto del virus sobre CPN humanas derivadas de células pluripotenciales inducidas (iPSC). A través de la técnica de TUNEL y de la detección de las caspasas 3 y 9, logró evidenciarse que las células que sufrían apoptosis eran mayoritariamente las que se encontraban infectadas 62 . Además, se evidenció que la apoptosis fue causada por disfunción mitocondrial y por estrés en el RE, dado que se detectó la liberación del citocromo c en citoplasma y encontraron fosforiladas proteínas involucradas en la vía de las UPRs, incluyendo PERK, JNK, IRE1α e IF2α 62 .…”
Section: Apoptosis Inducida Por CMV En El Sistema Nervioso Centralunclassified
“…También parece existir efecto diferentes según el modelo in vitro empleado, por el tipo de explante del cual las células son obtenidas y de sus condiciones de cultivo 58 . Por otra parte, estudios en monocitos y en CPN sugieren un fuerte efecto del estado de diferenciación celular 62,63,65 . De igual forma, resulta interesante que el virus emplea diversas estrategias para lograr un mismo cometido, ya que los miRNAs virales pueden actuar sinérgicamente con las proteínas virales para contrarrestar las defensas de la célula a la infección.…”
Section: Conclusionesunclassified