Blood genome expression Profiles in Infants with Congenital Cytomegalovirus Infection: Is the asymptomatic infant truly asymptomatic?
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PROVIDER: PRJNA422858 | ENA |
REPOSITORIES: ENA
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Project description:Background: Congenital cytomegalovirus (cCMV) infection represents the most frequent non-genetic cause of sensorineural hearing loss (SNHL). The disease spectrum varies from clinically apparent (“symptomatic”) to clinically inapparent (“asymptomatic”). Analysis of host genome expression profiles has provided new insights into disease pathogenesis and assessment of clinical severity. Its value as a biomarker in infants with cCMV has not been explored. Methods: Infants with cCMV infection, both symptomatic and asymptomatic, were enrolled at a median age of 17 days of age and followed up for 3 years to assess the development of SNHL. Healthy age matched controls were also enrolled as a reference. Blood samples were obtained at enrollment and follow-up to assess host responses by RNA transcriptional profiling. Symptomatic CMV was defined as the presence of any clinical, laboratory, ophthalmologic, audiologic or neuroimaging abnormalities.
2020-05-26 | GSE108211 | GEO
Project description:Background: Congenital cytomegalovirus (cCMV) is a common intrauterine infection, leading to neurodevelopmental disabilities. Early prognostic assessment of the severity of cCMV has remained an ongoing challenge. We aimed to identify amniotic fluid biomarkers of the severity of cCMV-related fetal brain injury. Methods: Global proteome analysis was performed in mid-gestation amniotic fluid samples, comparing fetuses with severe cCMV to asymptomatic CMV-infected fetuses (the discovery cohort). The levels of selected differentially-excreted proteins were further determined by specific immunoassays, and evaluated in an independent validation cohort, including clinically-blinded amniotic fluid of CMV-infected fetuses from unrelated centers. Findings: Proteome analysis identified 29 amniotic fluid proteins with distinct abundance in fetuses with severe-, compared to asymptomatic, cCMV. Pathway analysis of the differentially-excreted proteins revealed enriched pathways of inflammatory response, cellular compromise, immunological disease, organismal injury, and neurological disease, underlining a link between excessive inflammation at the maternal-fetal interface and the development of cCMV-related fetal brain damage. Importantly, the levels of two of these proteins, chemerin and galectin-3-binding protein (Gal-3BP), selected for validation, demonstrated 88.2% sensitivity (each), 100-96.2% specificity, 100-93.8% positive predictive value, and 92.9-92.6% negative predictive value, with 0.98-0.97 area under the curve (for chemerin - Gal-3BP, respectively) in differentiating 17 fetuses with severe cCMV from 26 asymptomatic CMV-infected fetuses. Interpretation: These results identify the immunomodulatory proteins chemerin and Gal-3BP as new highly predictive amniotic fluid biomarkers of cCMV severity, which could guide early prognostic stratification and potential personalized treatment of cCMV-infected fetuses. Funding: Israel Science Foundation; Research Fund of the Hadassah Medical Organization
2022-05-25 | PXD029105 | Pride
Project description:Human cytomegalovirus (HCMV) infection in infants cause severe diseases, such as neonatal hepatitis. However, the single-cell dimensional description of the immune cell alteration during the first virus exposure process in infants, remains poorly understood. The hepatocytes play an essential role in metabolic homeostasis and detoxification. The Concomitant Effects of CMV infection on liver lipid metabolism in infants are still unclear. Here, using single-cell RNA-sequencing, we found MCMV can infect most cell types of infant mice liver, changing the number of immune cells. MCMV infection increases proliferating CD8 effector T cells and a subset of Nos2+ monocytes, which may play important roles in the early anti-viral process. Furthermore, MCMV infection subvert the protein expression profile of lipid metabolism in hepatocytes. Overall, our data provide insights as to how the immune system response to MCMV infection during the early stage of infection, and the impact of infection on lipid metabolism in infant mice hepatocytes.
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Project description:UL4015-23 peptide in congenital cytomegalovirus infection
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Project description:We have employed whole genome microarray expression profiling to identify genes differentially expressed in neonatal bowel tissues of different gastrointestinal conditions. Bowel tissues were collected from infants who underwent surgery treatment for necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Infants with other non-inflammatory, congenital intestinal conditions were employed as the Surgical-Control. Differential whole genome microarray analysis was performed.
2014-01-21 | E-GEOD-46619 | biostudies-arrayexpress
Project description:We have employed miRNA microarray expression profiling to identify miRNA differentially expressed in neonatal bowel tissues with different gastrointestinal conditions. Bowel tissues were collected from infants who underwent surgery treatment for necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP). Infants with other non-inflammatory, congenital intestinal conditions were employed as the Surgical-Control. Differential miRNA microarray analysis was performed.
2015-08-24 | E-GEOD-68054 | biostudies-arrayexpress
Project description:Human cytomegalovirus (HCMV) infection in infants cause severe diseasessuch as neonata hepatitis, However, the single-cell dimensiona description otthe immune cel alteration during the first virus exposure process in infantsremains poorly understood. The hepatocytes play an essential role in metabolichomeostasis and detoxification, The Concomitant Effects of CMV infection oriver lipid metabolism in infants are still unclear. Here, using single-cell RNAsequencing, we found MCMV can infect most cell types of infant mice liverchanging the number of immune cells, MCMV infection increases proliferatincsubset of Nos2+CD8 effectorcells and amonocytes，which may plalimportant roles in the early anti-viral process. Furthermore, MCMV infectiorsubvert the protein expression profile of lipid metabolism in hepatocytesOverall, our data provide insights as to how the immune system response toMCMY infection during the early stage of infection, and the impact of infectionon lipid metabolism in infant mice hepatocvtes.
2023-03-13 | PXD040842 |
Project description:In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in babies who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of babies exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed babies, regardless of birth condition. Thus, the evaluation and monitoring of all exposed babies are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of molecular markers in infants exposed to ZIKV without CZS could provide valuable means to improve their clinical monitoring. Here, we used a shotgun-proteomic approach to investigate molecular markers in the serum of infants without CZS symptoms but exposed to ZIKV intrauterine (ZIKV) compared to non-exposed controls (CTRL).
2021-09-09 | PXD020294 | Pride
Project description:MicroRNA expression profiling of urine exosomes in children with congenital cytomegalovirus infection
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Project description:Cytomegalovirus (CMV) is the most common congenital infection worldwide, causing deafness and neurodevelopmental delay in infected infants. Preexisting maternal immunity to CMV is known to influence the incidence and severity of congenital infection. To establish the role of maternal antibody in protection against placental CMV transmission, 6 rhesus CMV (RhCMV)-seronegative rhesus monkey dams were CD4+ T cell depleted at the end of the first trimester of pregnancy and treated with either a single dose of standardly-produced hyperimmune globulin (HIG) (n=3) or a dose-optimized regimen of a potently-neutralizing HIG (n=3) prior to IV inoculation with a mixture of RhCMV strains. Passive infusion with HIG provided complete protection against fetal loss (0/6 HIG-treated vs. 5/6 control dams aborted; p=0.015). Furthermore, the dose-optimized, highly-neutralizing HIG product reduced the magnitude and diversity of maternal plasma RhCMV populations and inhibited placental transmission of RhCMV (0/3 transmitted), suggesting that pre-existing highly-neutralizing antibodies are sufficient to prevent congenital CMV infection and disease. In this study, we sought to investigate the placental transcriptome to determine whether: a) RhCMV congenital infection was being controlled at the level of the placenta, b) what genes are up-regulated following RhCMV congenital infection, and c) whether there are any genes associated with protection against viral infection.
2016-09-28 | GSE87395 | GEO