The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene

Hiroki Isomura, Mark F. Stinski, Takayuki Murata, Sanae Nakayama, Shigeki Chiba, Yoshiki Akatsuka, Teru Kanda, Tatsuya Tsurumi

Research output: Contribution to journalArticle

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Abstract

Background: Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein. Methodology/Principal Findings: To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth. Conclusions/Significance: While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV-infected cells.

Original languageEnglish
Article numbere11901
JournalPloS one
Volume5
Issue number7
DOIs
Publication statusPublished - 20-08-2010

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Human herpesvirus 5
Cytomegalovirus
Open Reading Frames
open reading frames
Genes
virus replication
Gene Expression
gene expression
Cell culture
Messenger RNA
Proteins
genes
Viral DNA
Immunosuppressive Agents
protein synthesis
Viruses
Gene expression
Packaging
Plasmids
cell culture

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Isomura, H., Stinski, M. F., Murata, T., Nakayama, S., Chiba, S., Akatsuka, Y., ... Tsurumi, T. (2010). The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene. PloS one, 5(7), [e11901]. https://doi.org/10.1371/journal.pone.0011901
Isomura, Hiroki ; Stinski, Mark F. ; Murata, Takayuki ; Nakayama, Sanae ; Chiba, Shigeki ; Akatsuka, Yoshiki ; Kanda, Teru ; Tsurumi, Tatsuya. / The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene. In: PloS one. 2010 ; Vol. 5, No. 7.
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abstract = "Background: Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein. Methodology/Principal Findings: To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth. Conclusions/Significance: While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV-infected cells.",
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Isomura, H, Stinski, MF, Murata, T, Nakayama, S, Chiba, S, Akatsuka, Y, Kanda, T & Tsurumi, T 2010, 'The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene', PloS one, vol. 5, no. 7, e11901. https://doi.org/10.1371/journal.pone.0011901

The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene. / Isomura, Hiroki; Stinski, Mark F.; Murata, Takayuki; Nakayama, Sanae; Chiba, Shigeki; Akatsuka, Yoshiki; Kanda, Teru; Tsurumi, Tatsuya.

In: PloS one, Vol. 5, No. 7, e11901, 20.08.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene

AU - Isomura, Hiroki

AU - Stinski, Mark F.

AU - Murata, Takayuki

AU - Nakayama, Sanae

AU - Chiba, Shigeki

AU - Akatsuka, Yoshiki

AU - Kanda, Teru

AU - Tsurumi, Tatsuya

PY - 2010/8/20

Y1 - 2010/8/20

N2 - Background: Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein. Methodology/Principal Findings: To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth. Conclusions/Significance: While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV-infected cells.

AB - Background: Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein. Methodology/Principal Findings: To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth. Conclusions/Significance: While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV-infected cells.

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