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Published on: July 6, 2013
Human cytomegalovirus UL144 gene polymorphisms in congenital infections
Olivier Picone1, Jean-Marc Costa, Marie-Laure Chaix
1Laboratoire de Virologie, EA 3620 Université René Descartes, CHU Necker-Enfants-Malades, 149 rue de Sèvres, 75015 Paris, France.
Abstract:
The human cytomegalovirus (HCMV) UL144 gene is a tumor necrosis factor-like receptor with the potential to affect HCMV virulence. HCMV strains display genetic variability in the UL144 region, and the analysis of a potential link between UL144 gene polymorphisms and disease severity has scarcely been studied. However, a correlation between the UL144 genotype and congenital-disease outcome has been reported in one previous study, with the observation that all asymptomatic infants had a single UL144 genotype. In order to confirm or refute this finding, we determined the UL144 polymorphisms of HCMV strains recovered from the amniotic fluids of 38 infected fetuses and compared them to HCMV strains obtained from 30 viremic adult controls. The UL144 sequences were distributed among five genotypes (A, B, C, AC, and AB), as previously described. We observed similar percentages of the three major genotypes A (37%), B (33%), and C (27%) in our population. The UL144 genotype distributions were similar among the group of infected adults and the group of infected fetuses and among symptomatic and asymptomatic fetuses (P < 0.05). In our series, all five UL144 genotypes could be vertically transmitted from mothers to fetuses, and all could cause symptomatic congenital infection. We concluded that determination of UL144 polymorphisms in cases of congenital infection is not relevant, since it is unlikely to help predict the outcome of the infection.
Insights
Human cytomegalovirus (HCMV) UL144 gene variations do not predict congenital infection outcomes. All identified UL144 genotypes can transmit from mother to fetus and cause symptomatic disease.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Human cytomegalovirus (HCMV) UL144 gene encodes a tumor necrosis factor-like receptor influencing viral virulence.
- Genetic variability exists within HCMV UL144 gene sequences.
- Previous studies suggested a link between UL144 genotype and congenital HCMV disease severity.
Purpose of the Study:
- To investigate the association between HCMV UL144 gene polymorphisms and congenital infection outcomes.
- To confirm or refute a prior study linking UL144 genotype to asymptomatic congenital HCMV infection.
Main Methods:
- Determined UL144 polymorphisms in HCMV strains from 38 infected fetuses and 30 adult controls.
- Compared UL144 genotype distributions between fetal and adult groups, and between symptomatic and asymptomatic fetuses.
- Analyzed vertical transmission of UL144 genotypes from mothers to fetuses.
Main Results:
- HCMV UL144 sequences clustered into five genotypes (A, B, C, AC, AB).
- Genotype distributions were similar across infected adults, infected fetuses, and symptomatic/asymptomatic fetuses (P < 0.05).
- All five UL144 genotypes were vertically transmitted and capable of causing symptomatic congenital infection.
Conclusions:
- UL144 gene polymorphisms do not reliably predict the outcome of congenital HCMV infections.
- Determining UL144 genotype is unlikely to aid in predicting congenital HCMV disease severity.
- HCMV UL144 genotype analysis is not clinically relevant for managing congenital infections.
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