title: Cytomegalovirus-induced brain malformations in fetuses.
abstract: Neurologic morbidity associated with congenital cytomegalovirus (CMV) infection is a major public health concern. The pathogenesis of cerebral lesions remains unclear. We report the neuropathologic substrates, the immune response, and the cellular targets of CMV in 16 infected human fetal brains aged 23 to 28.5 gestational weeks. Nine cases were microcephalic, 10 had extensive cortical lesions, 8 had hippocampal abnormalities, and 5 cases showed infection of the olfactory bulb. The density of CMV-immunolabeled cells correlated with the presence of microcephaly and the extent of brain abnormalities. Innate and adaptive immune responses were present but did not react against all CMV-infected cells. Cytomegalovirus infected all cell types but showed higher tropism for stem cells/radial glial cells. The results indicate that 2 main factors influence the neuropathologic outcome at this stage: the density of CMV-positive cells and the tropism of CMV for stem/progenitor cells. This suggests that the large spectrum of CMV-induced brain abnormalities is caused not only by tissue destruction but also by the particular vulnerability of stem cells during early brain development. Florid infection of the hippocampus and the olfactory bulb may expose these patients to the risk of neurocognitive and sensorineural handicap even in cases of infection at late stages of gestation.
authors.affiliation: From the Inserm (NT, A-LD, SK-S, JN, SC, ZC, TVDA, PG, HA-B); Univ Paris Diderot, Sorbonne Paris Cité (NT, A-LD, S-KS, JN, SC, TVDA, PG, HAB); Paediatric Otorhinolaryngology Department, Robert Debré Hospital (NT, TVDA); Department of Pathology, Sainte-Anne/Cochin Hospital (CF-B, A-LD); and Biology of Development Department, Robert Debré Hospital (A-LD, SK-S), Paris; Department of Pathology, Charles Nicolle Hospital, Rouen (AL); Department of Pathology, Morvan Hospital, Brest (PM); Obstetrics Department, Béclère Hospital, Clamart (OP); and Obstetrics Department, Foch Hospital, Suresnes (OP), France; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (JAG); Centre for the Developing Brain, King's College, St. Thomas' Campus, London, United Kingdom (PG); and Department of Pathology, Lariboisière Hospital, Paris, France (HA-B).
authors.forename: Natacha
authors.initials: N
authors.lastname: Teissier
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallet-Bianco
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Suonavy
authors.initials: S
authors.lastname: Khung-Savatovsky
authors.forename: Jeannette
authors.initials: J
authors.lastname: Nardelli
authors.forename: Sara
authors.initials: S
authors.lastname: Cipriani
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Csaba
authors.forename: Olivier
authors.initials: O
authors.lastname: Picone
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: Thierry
authors.initials: T
authors.lastname: Van Den Abbeele
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
mesh_terms: D001921:Brain / Q000196:embryology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000473:pathology*; D005333:Fetus; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen