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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HCMV is the leading cause of congenital infection, with 0.5-0.9% of infants affected in Europe, and primary maternal infection from the preconceptional phase to the first half of pregnancy bears the highest risk for long-term sequelae-like mental retardation, visual impairment, and progressive sensorineural hearing loss. As compared to couples conceiving spontaneously those under infertility treatment are well accessible to primary HCMV prevention. Since they face higher risk pregnancies this chance should be considered. The concept comprises serological screening for HCMV-IgG, including the partner where appropriate, defining individual risk factors, and counselling on hygiene at the initial assessment of infertility treatment. If seroconversion occurs, the subsequent treatment cycles should be postponed by 6 months. Uncertainties of diagnosis in early pregnancy which may lead to precautious elective termination can be prevented. A newborn at risk of congenital HCMV infection can be identified and scheduled for laboratory and paediatric evaluation within the first 2 weeks of life.
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PMID:Congenital HCMV and assisted reproduction: Why not use the chance for primary screening? 2643 54

CMV is the most common congenital infection in the United States. The major target of congenital CMV is the brain, with clinical manifestations including mental retardation, vision impairment, and sensorineural hearing loss. Previous reports have shown that CD8(+) T cells are required to control viral replication and significant numbers of CMV-specific CD8(+) T cells persist in the brain even after the initial infection has been cleared. However, the dynamics of CD8(+) T cells in the brain during latency remain largely undefined. In this report, we used TCR sequencing to track the development and maintenance of neonatal clonotypes in the brain and spleen of mice during chronic infection. Given the discontinuous nature of tissue-resident memory CD8(+) T cells, we hypothesized that neonatal TCR clonotypes would be locked in the brain and persist into adulthood. Surprisingly, we found that the Ag-specific T cell repertoire in neonatal-infected mice diversified during persistent infection in both the brain and spleen, while maintaining substantial similarity between the CD8(+) T cell populations in the brain and spleen in both early and late infection. However, despite the diversification of, and potential interchange between, the spleen and brain Ag-specific T cell repertoires, we observed that germline-encoded TCR clonotypes, characteristic of neonatal infection, persisted in the brain, albeit sometimes in low abundance. These results provide valuable insights into the evolution of CD8(+) T cell repertoires following neonatal CMV infection and thus have important implications for the development of therapeutic strategies to control CMV in early life.
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PMID:The Neonatal CD8+ T Cell Repertoire Rapidly Diversifies during Persistent Viral Infection. 2676 33

Human cytomegalovirus (HCMV) is the leading cause of congenital infections. Symptomatic newborns present with a range of sequelae including disorders of the CNS such as visual impairment, microcephaly, mental retardation and hearing loss. HCMV congenital infection causes gross changes in brain morphology and disturbances in glial and neuronal distribution, number and migration. In these studies, we have evaluated the effectiveness of the antiviral maribavir in inhibiting HCMV infections of ES cell-derived neuronal progenitor cells (NPC). We used EZ-spheres generated from H9 ES cells which are pre-rosette NPCs that retain long-term potential to differentiate into diverse central and peripheral neural lineages following directed differentiation. Our results demonstrate that the maribavir disrupts HCMV replication and viral yield in undifferentiated EZ-sphere-derived NPCs. In addition, we observed that maribavir limits HCMV replication and reduces the percentage of infected cells during differentiation of NPCs. Finally, early steps in differentiation are maintained during infection by treating with maribavir, likely an indirect effect resulting from decreased viral spread. Future studies of NPC proliferation and differentiation during infection treated with maribavir could provide the impetus for studying maribavir as an antiviral agent for congenital HCMV disease.
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PMID:Impact of a cytomegalovirus kinase inhibitor on infection and neuronal progenitor cell differentiation. 2687 88

Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells in vitro, indicating reduction of self-renewal and expansion of neural progenitors by IE2. At 2 days after in utero electroporation into the ventricle of the developing brain, a dramatically lower percentage of IE2-expressing cells was detected in the ventricular zone (VZ) and cortical plate (CP) compared to control cells, suggesting that IE2 concurrently dysregulates neural stem cell maintenance in the VZ and neuronal migration to the CP. In addition, most IE2+ cells in the lower intermediate zone either showed multipolar morphology with short neurites or possessed nonradially oriented processes, whereas control cells had long, radially oriented monopolar or bipolar neurites. IE2+ callosal axons also failed to cross the midline to form the corpus callosum. Furthermore, we provide molecular evidence that the cell cycle arrest and DNA binding activities of IE2 appear to be responsible for the increased neural stem cell exit from the VZ and cortical migrational defects, respectively. Collectively, our results demonstrate that IE2 disrupts the orderly process of brain development in a stepwise manner to further our understanding of neurodevelopmental HCMV pathogenesis.IMPORTANCE HCMV brain pathogenesis has been studied in limited experimental settings, such as in vitro HCMV infection of neural progenitor cells or in vivo murine CMV infection of the mouse brain. Here, we show that IE2 is a pivotal factor that contributes to HCMV-induced abnormalities in the context of the embryonic brain using an in utero gene transfer tool. Surprisingly, IE2, but not HCMV IE1 or murine CMV ie3, interferes pleiotropically with key neurodevelopmental processes, including neural stem cell regulation, proper positioning of migrating neurons, and the callosal axon projections important for communication between the hemispheres. Our data suggest that the wide spectrum of clinical outcomes, ranging from mental retardation to microcephaly, caused by congenital HCMV infection can be sufficiently explained in terms of IE2 action alone.
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PMID:Human Cytomegalovirus IE2 Protein Disturbs Brain Development by the Dysregulation of Neural Stem Cell Maintenance and the Polarization of Migrating Neurons. 2861 4

Maternofoetal infection with Cytomegalovirus (CMV) is the most common congenital infection and a leading cause of mental retardation and sensori-neural hearing loss. Population-based studies indicate that at least 0.5% of all infants born alive have CMV of whom approximately 10% have clinically evident symptomsat birth. The Justification of systematic screening for foetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when foetal infection has been diagnosed. In case of congenital CMV infection, infants can be symptomatic or asymptomatic at birth. Mortality for such infants can reach 30%, and survivors can have mental retardation, sensorineural hearing loss, chorioretinitis, and other significant medical problems. A newborn symptomatic is defined by the existence of clinical and / or biological signs and / or neonatal imaging, the most frequent clinical signs are: hepatosplenomegaly (60%), microcephaly (53%), jaundice (67%), petechiae (76%), at least one neurological abnormality (68%). The frequency of biological abnormalities is as follows: increase in transaminases (83%), thrombocytopenia (77%), hyperbilirubinemia (69%), haemolysis (51%), hyperproteinorrachy (46%). The abnormalities of neonatal imaging are present in 70% of symptomatic newborns; intracerebral calcifications are the most frequent abnormalities. We report a case of newborn who presented a congenital infection by CMV, evoked on the intrauterine growth retardation, organs of the reticulo endothelial and haematological system were reached while nervous system was spared, and CMV PCR was very positive. indicating an antiviral treatment for 6weeks based on ganciclovir.
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PMID:Severe neonatal cytomegalovirus infection: about a case. 2890 89


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