Human Cytomegalovirus UL144 Gene Polymorphisms in Congenital Infections

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.

Human Cytomegalovirus UL144 Is Associated with Viremia and Infant Development Sequelae in Congenital Infection

“…Molecular epidemiology based on the UL144 gene has been carried out in Italian (1, 2), French (18,19), American (3,16), and Japanese (25) populations. In our geographically distinct Irish cCMV population, UL144 A was the most prevalent, followed closely by UL144 B.…”

“…In addition, genotype UL144 C was linked to termination of pregnancy following detection of HCMV in the amniotic fluid (1). In direct contrast, UL144 genetic polymorphisms were associated with neither clinical presentation nor viral-load levels in the amniotic fluid in a French population (18,19). Furthermore, Bale and colleagues found no relationship between the UL144 genotype and the congenital clinical outcome (3).…”

Transmission of cytomegalovirus via breast milk in extremely premature infants

“…The following PCR primers were used: outer forward primer (5 0 -TCGTATTACAAACCGCGGAGAG GAT-3 0 ), outer reverse primer (5 0 -ACTCAGACACGGTTCCGTAA-3 0 ), inner forward primer (5 0 -CTTCCGGTAGGCATGAA-3 0 ) and inner reverse primer (5 0 -GACTTAATCGTACCGTGA-3 0 ). 16 The PCR products were sequenced directly using a BigDye Terminator Cycle Sequence Kit and ABI PRISM 3100 Automated Sequencer (Applied Biosystems).…”

UL146 variability among clinical isolates of Human Cytomegalovirus from Japan

“…It is suggested that the UL133-UL151 region is important in immune response evasion and might be involved in some of the pathogenic properties ascribed to HCMV . For instance, the sequence of the UL144 ORF, reported to encode a tumor necrosis factor analogue, amplified from clinical samples clustered in five defined phylogenetic groups (Lurain et al, 1999;Murayama et al, 2005;Picone et al, 2005). The UL139 gene was shown to be highly polymorphic and the UL139 sequences clustered in six groups, in which various nucleotide insertions and non-synonymous substitutions were detected .…”