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Published on: December 29, 2015
UL146 variability among clinical isolates of human cytomegalovirus from Japan
Francisco Aguayo1, Tsugiya Murayama, Yoshito Eizuru
1Molecular Pathology and Epidemiology laboratory, Centro de Investigaciones Médicas, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. faguayo@med.uchile.cl
Abstract:
Human cytomegalovirus (HCMV) is a herpesvirus associated with serious diseases in immunocompromised subjects. The region between ORF UL133 and UL151 from HCMV, named ULb' is frequently deleted in attenuated AD169 and in highly passaged laboratory strains. However, this region is conserved in low-passaged and more virulent HCMV, like the Toledo strain. The UL146 gene, which is located in the ULb' region, encodes a CXC-chemokine analogue. The diversity of UL146 gene was evaluated among fifty-six clinical isolates of HCMV from Japan. Results show that UL146 gene was successfully amplified by the polymerase chain reaction (PCR) in only 17/56 strains (30%), while the success rate for UL145/UL147 gene was 18/56 strains (32%). After DNA sequencing, the 35 amplified strains were classified into 8 groups. When compared, variability of UL146 ranged from 25.1% to 52.9% at the DNA level and from 34.5% to 67% at the amino acid level. Seven groups had the interleukin-8 (IL-8) motif ERL (Glu-Leu-Arg) CXC and one group had only the CXC motif, suggesting the absence of the IL-8 function of UL146. In conclusion, we found that UL146 gene of HCMV is hyper-variable in clinical strains from Japan suggesting the possibility of a different function in each sequence group.
Insights
The Human Cytomegalovirus (HCMV) UL146 gene shows high variability in Japanese clinical isolates. This hypervariability suggests diverse functions among different HCMV sequence groups.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Human cytomegalovirus (HCMV) is a herpesvirus causing severe illness in immunocompromised individuals.
- The ULb' region, including the UL146 gene, is often deleted in lab strains but conserved in virulent HCMV.
- The UL146 gene encodes a CXC-chemokine analogue.
Purpose of the Study:
- To evaluate the genetic diversity of the UL146 gene in clinical HCMV isolates from Japan.
- To understand the implications of UL146 gene variability on its function.
Main Methods:
- Polymerase chain reaction (PCR) amplification of the UL146 gene from 56 clinical HCMV isolates.
- DNA sequencing of amplified UL146 gene fragments.
- Comparative analysis of DNA and amino acid sequences to determine variability and identify functional motifs.
Main Results:
- Successful amplification of UL146 was achieved in 30% of strains; UL145/UL147 in 32%.
- Sequencing revealed 8 distinct groups with UL146 DNA variability from 25.1% to 52.9% and amino acid variability from 34.5% to 67%.
- Seven groups possessed the interleukin-8 (IL-8) ERL CXC motif, while one group only had the CXC motif, indicating a potential loss of IL-8 function.
Conclusions:
- The UL146 gene in HCMV clinical strains from Japan exhibits significant hypervariability.
- This genetic diversity suggests that UL146 may have distinct functions depending on the specific sequence group.
- Further research is needed to elucidate the functional implications of UL146 hypervariability in HCMV pathogenesis.
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