Volume 164, July 2023, 105490Author links open overlay panel, , , , , , , , , , AbstractBackground

Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among newborns worldwide. Although both the host's and the virus’ genetic backgrounds contribute to the outcome of infections, significant gaps remain in our understanding of the exact mechanisms that determine disease severity.

Objectives

In this study, we sought to identify a correlation between the virological features of different HCMV strains with the clinical and pathological features of congenitally infected newborns, therefore proposing new possible prognostic factors.

Study design

This short communication presents five newborns with congenital cytomegalovirus infection, whose clinical phenotype during fetal, neonatal, and follow-up periods is correlated with in-vitro growth properties, immunomodulatory abilities and genome variability of HCMV strains isolated from organic samples (urine) of the patients.

Results

The five patients described in this short communication displayed a heterogeneous clinical phenotype and different virus replication properties, immunomodulatory abilities, and genetic polymorphisms. Interestingly, we observed that an attenuate viral replication in-vitro influences the immunomodulatory abilities of HCMV, leading to more severe congenital infections and long-term sequelae. Conversely, infection with viruses characterized by aggressive replicative behavior in-vitro resulted in asymptomatic patients’ phenotypes.

Conclusions

Overall, this case series suggests the hypothesis that genetic variability and differences in the replicative behavior of HCMV strains result in clinical phenotypes of different severity, most likely due to different immunomodulatory properties of the virus.

Section snippetsBackground

Human cytomegalovirus (HCMV) is a double-stranded DNA virus characterized by unique molecular and epidemiological properties, wide seroprevalence, and lifelong persistence within the infected hosts. A paradigmatic example of the significant clinical importance of HCMV is congenital CMV (cCMV) infection in newborns [1], [2], [3], currently the major infectious cause of sensorineural hearing loss and neurodevelopmental delays in children born in developed countries. The severity of the clinical

Objectives

In this study, we sought to propose a possible explanation for the difference of manifestation of congenital HCMV infections in newborns and, therefore, present new possible prognostic factors.

Study design

We present a case series of five newborns with cCMV infection, whose clinical features displayed during fetal, neonatal, and follow-up period were explained and correlated with replicative characteristics, immunomodulatory abilities, and genetical variability of different strains of HCMV, isolated from a sample of their urine, prelevated during medical examination.

Replicativebehaviorr, immunomodulatory abilities and genetical variability were assessed during previous studies [10,11], analysing

Results

Replicative behavior, immunomodulatory ability and genetical variability of the HCMV strains, alongside the most salient clinical and pathological features of the five newborns reported in this case series (indicated as P) are summarized in Table 1.

Patients 6 and 10 resulted to be infected by HCMV strains which displayed slow-replicating behavior, induced in infected cells a normal expression of NK-cells activating ligands (PVR/CD155, MICA, ULBP 2/5/6, ULBP3) in HFF infected cells and did not

Discussion

The variability in the clinical presentations in HCMV congenitally infected newborns is still a matter of debate [9], [10], [11]. Even though it is known that the trimester of infection influences the severity of infection, the mechanisms underlying the main differences in clinical phenotype are only partially described and understood. In this study, we presented a case series of five newborns with cCMV infection, characterized by heterogeneous clinical features during fetal, neonatal, and

Funding

This research was funded by “Cassa di Risparmio” Foundation of Turin (RF = 2019.2273 to V.D.O.).

Access to data

The datasets used and/or analyzed during the current study are available from the first author on request.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Research Ethics Committee of the University Hospital of Turin “A.O.U. Città della Salute e della Scienza di Torino – A.O. Ordine Mauriziano – A.S.L. TO1” (No. 007816).

Consent to participate

Written informed consent was obtained from all the participants’ legal guardians.

CRediT authorship contribution statement

Alessia Spadavecchia: Conceptualization, Data curation, Formal analysis, Methodology. Francesco Cresi: Formal analysis. Agata Leone: Conceptualization, Data curation. Valentina Dell'Oste: Conceptualization, Funding acquisition. Matteo Biolatti: Methodology. Ganna Galitska: Methodology. Alessandra Coscia: Data curation. Sonia Deantoni: Data curation, Methodology. Cinzia Valenza: Data curation, Methodology. Enrico Bertino: Conceptualization. Chiara Peila: Data curation.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We would sincerely like to thank Matthew Christian Metzger for his critical reading of our manuscript.

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