Polymorphisms of human cytomegalovirus UL148A, UL148B, UL148C, UL148D genes in clinical strains.

摘要

BACKGROUND: Clinical isolates of human cytomegalovirus (HCMV) display polymorphisms in multiple genes. Some authors have suggested that polymorphisms are implicated in HCMV-induced immunopathogenesis, as well as in strain-specific behaviors, such as tissue-tropism and the ability to establish persistent or latent infections. OBJECTIVE: To describe the features of HCMV UL148A, UL148B, UL148C and UL148D open reading frames (ORFs) and the variable sites within the frames in clinical strains. STUDY DESIGN: PCR was performed to amplify these ORFs in 22 clinical strains. PCR amplification products were sequenced directly and analyzed. RESULTS: The nucleotide diversity of UL148A, UL148B, UL148C and UL148D ORFs in studied strains is 0.5-8.3%, 0.5-4.6%, 0.5-3% and 1.7-8.1%, respectively; the amino acid diversity of their putative proteins is 1.3-6.3%, 1.3-5.0%, 1.3-3.9% and 1.7-8.1%, respectively, related to the Merlin strain. The modification sites of UL148A, UL148B, UL148C and UL148D predicted proteins from strains in unpassaged urine samples were conserved, except for strain U96, compared with that of the Merlin strain. By phylogenetic and statistical analysis, the UL148A and UL148D sequences of clinical strains were classified into three groups. CONCLUSION: Compared to the UL148A, UL148B and UL148D ORFs, the UL148C ORF was relatively conserved, as was the amino acid sequence of the UL148C putative protein. Isolates that have been passaged several times in human embryonic lung fibroblasts (HELF) showed some changes of modification sites, however. A discrete linkage was found between the groups of UL148A gene and those of UL148D gene.