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Characterization of the murine cytomegalovirus genes encoding the major DNA binding protein and the ICP18.5 homolog
M Messerle1, G M Keil, K Schneider
1Department of Virology, University of Ulm, Germany.
Abstract:
In several herpesviruses the genes for the major DNA binding protein (MDBP), a putative assembly protein, the glycoprotein B (gB), and the viral DNA polymerase (pol) collocate. In murine cytomegalovirus (MCMV), two members of this gene block, pol (Elliott, Clark, Jaquish, and Spector, 1991, Virology 185, 169-186) and gB (Rapp, Messerle, Bühler, Tannheimer, Keil, and Koszinowski, 1992, J. Virol., 66, 4399-4406) have been characterized. Here the two other MCMV genes are characterized, the gene encoding the MDBP and the ICP18.5 homolog encoding a putative assembly protein. Like in human cytomegalovirus (HCMV) the genes order is pol, gB, ICP18.5, and MDBP. The 4.2-kb MDBP mRNA is expressed first in the early phase, whereas the 3.0-kb ICP18.5 mRNA is a late transcript. The open reading frame of the MDBP gene has the capacity of encoding a protein of 1191 amino acids with a predicted molecular mass of 131.7 kDa. The MCMV ICP18.5 ORF is translated into a polypeptide of 798 amino acids with a calculated molecular mass of 89.1 kDa. Comparison of the amino acid sequences of the predicted proteins of MCMV with the respective proteins of HCMV, Epstein-Barr virus (EBV), and herpes simplex virus type-1 (HSV-1) reveals a striking homology ranging from 72% (HCMV), 50% (EBV), to 45% (HSV-1) for the MDBP sequence and from 74% (HCMV), 51% (EBV), to 49% (HSV-1) for the ICP18.5 sequence. These results establish the close relationship of the two cytomegaloviruses, and underline the usefulness of the murine model for studies on the biology of the CMV infection.
Insights
This study characterizes two key genes in murine cytomegalovirus (MCMV), the major DNA binding protein (MDBP) and ICP18.5. Findings reveal significant homology with human cytomegalovirus, supporting MCMV as a model for CMV infection research.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Herpesviruses often share gene arrangements for key proteins like DNA polymerase (pol), glycoprotein B (gB), major DNA binding protein (MDBP), and assembly proteins.
- Murine cytomegalovirus (MCMV) has had its pol and gB genes previously characterized.
- The genes for MDBP and ICP18.5 (a homolog of an assembly protein) in MCMV remained to be fully elucidated.
Purpose of the Study:
- To characterize the MCMV genes encoding the major DNA binding protein (MDBP) and the ICP18.5 homolog.
- To determine the gene order and expression patterns of these MCMV genes.
- To compare the deduced amino acid sequences with homologous proteins from other herpesviruses.
Main Methods:
- Gene characterization of MCMV MDBP and ICP18.5.
- Analysis of mRNA expression timing (early vs. late).
- Amino acid sequence comparison with human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and herpes simplex virus type-1 (HSV-1).
Main Results:
- The MCMV gene order was confirmed as pol, gB, ICP18.5, and MDBP.
- MDBP mRNA (4.2-kb) is an early transcript, while ICP18.5 mRNA (3.0-kb) is a late transcript.
- High sequence homology was observed: MDBP (72% with HCMV) and ICP18.5 (74% with HCMV).
Conclusions:
- The characterized MCMV genes exhibit significant homology to their human cytomegalovirus (HCMV) counterparts.
- The findings reinforce the close evolutionary relationship between MCMV and HCMV.
- The study highlights the utility of the murine cytomegalovirus model for investigating cytomegalovirus biology.