Expression of human cytomegalovirus UL36 and UL37 genes is required for viral DNA replication
| Autor: | G S Pari, J A Smith |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Gene Expression Regulation
Viral Genes Viral DNA polymerase II viruses Immunology Molecular Sequence Data Restriction Mapping Cytomegalovirus Eukaryotic DNA replication Virus Replication Microbiology DNA polymerase delta Immediate-Early Proteins DNA replication factor CDT1 Viral Proteins Replication factor C Control of chromosome duplication Virology Amino Acid Sequence RNA Messenger DNA Primers Viral Structural Proteins biology Base Sequence DNA replication Molecular biology Viral replication Insect Science DNA Viral biology.protein Trans-Activators RNA Viral Research Article |
| Zdroj: | Journal of virology. 69(3) |
| ISSN: | 0022-538X |
| Popis: | It was previously reported that the region encoding human cytomegalovirus (HCMV) genes UL36 to UL38 was required for origin-dependent DNA replication. These genes encode transactivators that upregulate viral and cellular transcription. However, their requirement for viral DNA replication has not been demonstrated. We have now used an antisense phosphorothioate oligonucleotide complementary to the intron-exon boundary of the UL36 and UL37 unspliced RNA to show that these gene products are required for HCMV DNA replication. Southern analysis showed that this oligonucleotide almost completely inhibits HCMV DNA replication when used at concentrations as low as 0.08 microM. The ability of this oligonucleotide to inhibit DNA replication was not the result of an inhibition of virus adsorption. Southern blots showed no impairment of viral adsorption or internalization in the presence of either specific or nonspecific phosphorothioate oligonucleotides. In addition, Northern (RNA) blots confirm that this antisense compound specifically reduced UL36 mRNA in treated cells to undetectable levels while the steady-state levels of immediate-early transcripts IE1 and IE2 were unaffected. These results demonstrate that the UL36 and UL37 gene products provide an essential function in initiation of HCMV DNA replication. |
| Databáze: | OpenAIRE |
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