Blood genome expression profiles in infants with congenital cytomegalovirus infection

Ouellette, Christopher P.; Sánchez, Pablo J.; Xu, Zhaohui; Blankenship, Derek; Zeray, Fiker; Ronchi, Andrea; Shimamura, Masako; Chaussabel, Damien; Lee, Lizette; Owen, Kris E.; Shoup, Angela G.; Ramilo, Octavio; Mejías, Asunción

doi:10.1038/s41467-020-17178-5

Cited by 24 publications

(23 citation statements)

References 43 publications

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“…The complexity of this infection is perhaps best illustrated by a recent report describing different phenotypes of monozygotic twins with cCMV infections of which most were monochorionic [ 29 ]. Furthermore, recent findings from a transcriptomic study of infants with symptomatic and asymptomatic cCMV infections failed to define a pattern of gene expression that could distinguish these two clinical phenotypes, although it should be noted that this study cataloged transcriptomic patterns in peripheral blood cells and not in cells from target tissues such as the CNS [ 30 ]. Together, these data suggest that the CNS sequelae associated with cCMV infection likely represent a continuum and cannot be represented by a simple binary clinical classification of symptomatic and asymptomatic cCMV infection.…”

Section: Central Nervous System Disease Following Congenital Hcmv Infectionsmentioning

confidence: 99%

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Moulden¹,

Sung

Brizić

et al. 2021

Pathogens

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Human cytomegalovirus infection of the developing fetus is a leading cause of neurodevelopmental disorders in infants and children, leading to long-term neurological sequela in a significant number of infected children. Current understanding of the neuropathogenesis of this intrauterine infection is limited because of the complexity of this infection, which includes maternal immunological responses that are overlaid on virus replication in the CNS during neurodevelopment. Furthermore, available data from human cases are observational, and tissues from autopsy studies have been derived from only the most severe infections. Animal models of this human infection are also limited by the strict species specificity of cytomegaloviruses. However, informative models including non-human primates and small animal models have been developed. These include several different murine models of congenital HCMV infection for the study of CMV neuropathogenesis. Although individual murine models do not completely recapitulate all aspects of the human infection, each model has provided significant information that has extended current understanding of the neuropathogenesis of this human infection. This review will compare and contrast different murine models in the context of available information from human studies of CNS disease following congenital HCMV infections.

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Section: Central Nervous System Disease Following Congenital Hcmv Infectionsmentioning

confidence: 99%

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Moulden¹,

Sung

Brizić

et al. 2021

Pathogens

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“…A wide range of molecular and cellular profiling assays are currently available for the study of the human immune response [9]. Of all the omics technologies available, transcriptomic approaches are the most scalable, have the most breadth and robustness, and therefore appear to be best suited for the study of infectious diseases in children and adults [5 ▪▪ ,10–13]. The transcriptome represents the complement of RNAs (messenger-m-RNA) that are transcribed from the genome.…”

Section: Host Transcriptional Signatures For the Diagnosis Of Infecti...mentioning

confidence: 99%

“…In the quest for biomarkers of SNHL, a small study analysed host transcriptional profiling from blood spots in children with congenital CMV, and identified a preliminary signature that was associated with long term sequelae [40]. A subsequent larger study analysed the whole blood transcriptome in neonates with symptomatic and asymptomatic cCMV infection [5 ▪▪ ]. Unexpectedly, the study showed that the biosignatures of infants with symptomatic and asymptomatic cCMV disease were similar.…”

Section: Congenital and Perinatal Infectionsmentioning

confidence: 99%

“…In addition, the increased frequency of both community and hospital-acquired infections caused by multidrug-resistant pathogens highlight the challenges that physicians encounter when managing patients with infectious diseases [3]. Moreover, a number of infections can trigger the development of long-term sequelae such as post-respiratory syncytial virus (RSV) recurrent wheezing/asthma [4], late-onset sensorineural hearing loss in infants with congenital cytomegalovirus (CMV) infection [5 ▪▪ ] or COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) [6]. Altogether, these data emphasize the need for improved diagnostic and prognostic tools for optimal patient classification that enable more effective application of targeted antiinfective and immunomodulatory therapies in the clinical setting…”

Section: Introductionmentioning

confidence: 99%

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Host transcriptional signatures as predictive markers of infection in children

Mejías

Cohen²,

Glowinski³

et al. 2021

Current Opinion in Infectious Diseases

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Purpose of review Analyses of the host transcriptional response to infection has proved to be an alternative diagnostic strategy to standard direct pathogen detection. This review summarizes the value of applying blood and mucosal transcriptome analyses for the diagnosis and management of children with viral and bacterial infections. Recent findings Over the years, studies have validated the concept that RNA transcriptional profiles derived from children with infectious diseases carry a pathogen-specific biosignature that can be qualitatively and quantitively measured. These biosignatures can be translated into a biologically meaningful context to improve patient diagnosis, as seen in children with tuberculosis, rhinovirus infections, febrile infants and children with pneumonia; understand disease pathogenesis (i.e. congenital CMV) and objectively classify patients according to clinical severity (i.e. respiratory syncytial virus). Summary The global assessment of host RNA transcriptional immune responses has improved our understanding of the host-pathogen interactions in the clinical setting. It has shown the potential to be used in clinical situations wherein our current diagnostic tools are inadequate, guiding the diagnosis and classification of children with infectious diseases.

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“…This issue is quite challenging since current recommendations stipulate that all infants with cCMV infection must undergo periodic hearing surveillance testing for years. Recently, Ouellette et al identified a 16-gene classifier signature associated with the development of SNHL with 92% accuracy in 80 infants with cCMV infection. These promising results are the impetus for an upcoming National Institutes of Health–funded observational trial to evaluate blood transcriptional profiles as a potential biomarker for SNHL (DMID 21-0034).…”

mentioning

confidence: 99%

Detecting Hearing Loss in a Child With Congenital Cytomegalovirus Infection—Finding the Elusive Needle in the Haystack

Park

2023

JAMA Otolaryngol Head Neck Surg

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Congenital cytomegalovirus (cCMV) is the most common infectious cause of sensorineural hearing loss (SNHL). 1 It is estimated to account for up to 25% of SNHL in young children and is capricious in its presentation. 2 A substantial proportion of infants with cCMV infection will have normal hearing at birth and then present later with fluctuating or progressively worse hearing. However, not all children with cCMV infection will present with or develop late-onset SNHL; determining those at risk to develop this sequela has been an elusive goal.In this issue of JAMA Otolaryngology-Head & Neck Surgery, De Cuyper et al 3 report on the risk factors for congenital hearing loss in newborns with cCMV using a prospective multicenter registry. They identified 1033 children, 40.3% of whom were diagnosed with clinically apparent symptomatic and 59.7% with asymptomatic cCMV infection. Symptomatic disease was defined as containing clinical, neurological, or laboratory abnormalities. They included intrauterine growth retardation, petechiae, hepatosplenomegaly, thrombocytopenia, anemia, leukopenia, elevated transaminase levels, cholestasis, seizures, microcephaly, chorioretinitis, central nervous system imaging abnormalities, or SNHL. They found 3 independent risk factors for congenital SNHL in the symptomatic group: petechiae, periventricular cysts seen on brain magnetic resonance imaging (MRI), and maternal seroconversion of anti-CMV antibodies during the first trimester of pregnancy. For the asymptomatic group, they noted only 1 independent risk factor, first trimester maternal seroconversion. In addition, they found that the median viral load was markedly lower in children without congenital SNHL compared with those with hearing loss.These findings build on earlier smaller studies that just focused on symptomatic disease. [4][5][6] The association of first trimester seroconversion with SNHL, the significance of periventricular cysts on a brain MRI, and the identification of a risk factor for congenital SNHL in infants with asymptomatic cCMV infection are novel findings. 3 Another strength of this study is their use of a standardized registry created in 2007. A multidisciplinary team of pediatricians and otolaryngologists partnered with 6 centers to create a protocol for cCMV diagnosis, treatment, follow-up, and documentation. From this work, an astounding 1033 infants with cCMV infection were able to be diagnosed and evaluated for this project. As many US and Canadian institutions, some at the state or provincial level, are developing or refining their early CMV screening or testing ef-

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Blood genome expression profiles in infants with congenital cytomegalovirus infection

Cited by 24 publications

References 43 publications

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Host transcriptional signatures as predictive markers of infection in children

Detecting Hearing Loss in a Child With Congenital Cytomegalovirus Infection—Finding the Elusive Needle in the Haystack

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