Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Murine Cytomegalovirus Protein pM79 is a Key Regulator for Viral Late Transcription

ABSTRACT: We characterized the role of the conserved murine cytomegalovirus (MCMV) gene M79. Using a recombinant MCMV virus carrying a tagged M79 coding sequence, we showed that M79 encoded a protein (pM79) which was expressed at late times of infection and localized to nuclear viral replication compartments. M79 transcription was largely dependent on viral DNA synthesis but was markedly stimulated by pM79, suggesting a positive feedback loop. To investigate its role, we created the recombinant virus SMin79, in which the M79 coding sequence was disrupted by an 88-nt insertion. We subsequently repaired the mutation to generate marker-rescued virus SMrev79. While SMrev79 grew efficiently in fibroblasts, SMin79 failed to produce infectious progeny but was rescued by pM79 expression in trans. During SMin79 infection, representative viral immediate early and early gene products, as well as viral DNA, accumulated efficiently. Formation of viral replication compartments also appeared normal. Pulsed field gel electrophoresis analysis indicated that the overall structure of replicating viral DNA was indistinguishable in cells infected with SMin79 compared to that with wild type virus. However, the accumulation of viral products for late gene M55 was severely compromised. Viral oligonucleotide tiled array analysis revealed that the accumulation of many late transcripts, defined by their sensitivity to viral DNA synthesis inhibitor phosphonoacetic acid, was markedly reduced by pM79 mutation. This study extends our previous work to suggest that cytomegaloviruses use a conserved mechanism to promote transcription at late stages of infection, and that pM79 regulates expression of a subset of viral DNA synthesis-dependent transcripts. This study consists of 4 unreplicated samples. RNA from Mock-infected, WT infected, WT infected in the presence of PAA, and a mutant M79 version of MCMV.

ORGANISM(S): Mus musculus

SUBMITTER: travis Chapa

PROVIDER: E-GEOD-47586 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Murine Cytomegalovirus Protein pM79 is a Key Regulator for Viral Late Transcription

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