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

Human cytomegalovirus (HCMV) infects a number of organs and cell types in v ivo, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variants. A potential component of HCMV varian t strains is the UL144 open reading frame (ORF), which encodes a homologue of the herpesvirus entry mediator, HveA, a member of the tumor necrosis fac tor receptor superfamily. Sequence analysis of the UL144 ORF in 45 low-pass age clinical isolates demonstrated significant strain-specific variability. In individual isolates, nucleotide substitutions occur at up to 21% of the 531 positions, resulting in approximately the same percentage of substitut ions in the predicted 176-amino-acid sequence. Phylogenetic analysis indica ted that the nucleotide and amino acid sequences diverge into three major g roups. For genotypic comparison, the known hypervariable region encompassin g the proteolytic cleavage site of the glycoprotein B (gB) gene was also se quenced. All of the isolates could be typed according to the four known gB groups; hoc-ever, the gB and UL144 sequence groups appeared to be phylogene tically unlinked. The predicted UL144 product homology with tumor necrosis factor receptor family members, along with the unexpectedly high level of s equence variability of the UL144 ORF, suggests that the predicted product m ay play a role in HCMV infectivity and subsequent host disease.