Human cytomegalovirus UL144 open reading frame: sequence hypervariability in low-passage clinical isolates

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Human cytomegalovirus (HCMV) exhibits diverse tissue tropism and disease patterns in vivo.
• The UL144 open reading frame (ORF) in HCMV encodes a homologue of herpesvirus entry mediator A (HveA), a tumor necrosis factor receptor superfamily member.
• HCMV strain variability is hypothesized to influence disease and tissue tropism.

Purpose of the Study:

• To investigate the sequence variability of the HCMV UL144 ORF in clinical isolates.
• To determine the phylogenetic relationships of UL144 variants.
• To compare UL144 variability with that of the glycoprotein B (gB) gene.

Main Methods:

• Sequence analysis of the UL144 ORF from 45 low-passage HCMV clinical isolates.
• Phylogenetic analysis of nucleotide and amino acid sequences.
• Sequencing of the glycoprotein B (gB) hypervariable region for genotypic comparison.

Main Results:

• Significant strain-specific sequence variability was observed in the UL144 ORF, with up to 21% nucleotide and amino acid substitutions.
• Phylogenetic analysis revealed three major divergent groups for UL144 sequences.
• While all isolates could be typed into four known gB groups, UL144 and gB phylogenetic groups were unlinked.

Conclusions:

• The high sequence variability of the HCMV UL144 ORF suggests its potential role in HCMV infectivity and pathogenesis.
• The UL144 product's homology to tumor necrosis factor receptors further supports its involvement in host-virus interactions.
• UL144 and gB genetic variations appear to evolve independently, indicating distinct evolutionary pressures or functional roles.