Dataset Information

Transcription of true late (?2) cytomegalovirus genes requires UL92 function that is conserved among beta- and gammaherpesviruses.

ABSTRACT: Human cytomegalovirus-encoded UL92 plays an essential role in viral replication that has not been resolved. We show here that this gene controls the accumulation of true late (?2) viral transcripts, a property shared with several other recently evaluated genes (UL79, UL87, UL91, and UL95) conserved among beta- and gammaherpesviruses. When the UL92 mutant virus was evaluated, function was fully complemented by either the natural protein or the homologous Rh127 protein from rhesus cytomegalovirus. N-terminal epitope-tagged UL92 protein is functional, follows complex early-late expression kinetics, and localizes in the nucleus within viral replication compartments. UL92 severely impacts the late (72-h postinfection) expression of nine genes encoding virion proteins (UL32, UL55, UL73, UL75, UL80, UL86, UL99, and UL115), as well as UL91 and itself, but does not influence the levels of UL44, UL82, or UL83 accumulation. Although viral DNA is made at normal levels, viral capsid accumulation in the nucleus is severely compromised in UL92 mutant virus-infected cells, and mature virions are not observed in the cytoplasm. Taken together, UL92 is a key regulator of late viral gene expression, apparently functioning with four other beta- or gammaherpesvirus gene products in a pattern that appears reminiscent of gene regulation in T4 DNA bacteriophage.

SUBMITTER: Omoto S

PROVIDER: S-EPMC3911701 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcription of true late (γ2) cytomegalovirus genes requires UL92 function that is conserved among beta- and gammaherpesviruses.

Omoto Shinya S Mocarski Edward S ES

Journal of virology 20131016 1

Human cytomegalovirus-encoded UL92 plays an essential role in viral replication that has not been resolved. We show here that this gene controls the accumulation of true late (γ2) viral transcripts, a property shared with several other recently evaluated genes (UL79, UL87, UL91, and UL95) conserved among beta- and gammaherpesviruses. When the UL92 mutant virus was evaluated, function was fully complemented by either the natural protein or the homologous Rh127 protein from rhesus cytomegalovirus. ...[more]

PMID: 24131715

Similar Datasets

Project description:The catalytic site of the HIV integrase is contained within an RNase H-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. Herpes simplex virus (HSV) encodes two proteins with potential RNase H-like folds, the infected cell protein 8 (ICP8) DNA-binding protein, which is necessary for viral DNA replication and exhibits recombinase activity in vitro, and the viral terminase, which is essential for viral DNA cleavage and packaging. Therefore, we hypothesized that HIV integrase inhibitors might also inhibit HSV replication by targeting ICP8 and/or the terminase. To test this, we evaluated the effect of 118-D-24, a potent HIV integrase inhibitor, on HSV replication. We found that 118-D-24 inhibited HSV-1 replication in cell culture at submillimolar concentrations. To identify more potent inhibitors of HSV replication, we screened a panel of integrase inhibitors, and one compound with greater anti-HSV-1 activity, XZ45, was chosen for further analysis. XZ45 significantly inhibited HSV-1 and HSV-2 replication in different cell types, with 50% inhibitory concentrations that were approximately 1 µM, but exhibited low cytotoxicity, with a 50% cytotoxic concentration greater than 500 µM. XZ45 blocked HSV viral DNA replication and late gene expression. XZ45 also inhibited viral recombination in infected cells and ICP8 recombinase activity in vitro. Furthermore, XZ45 inhibited human cytomegalovirus replication and induction of Kaposi's sarcoma herpesvirus from latent infection. Our results argue that inhibitors of enzymes with RNase H-like folds may represent a general antiviral strategy, which is useful not only against HIV but also against herpesviruses. Importance: The herpesviruses cause considerable morbidity and mortality. Nucleoside analogs have served as effective antiviral agents against the herpesviruses, but resistance can arise through viral mutation. Second-line anti-herpes drugs have limitations in terms of pharmacokinetic properties and/or toxicity, so there is a great need for additional drugs for treatment of herpesviral infections. This study showed that the HIV integrase inhibitors also block herpesviral infection, raising the important potential of a new class of anti-herpes drugs and the prospect of drugs that combat both HIV and the herpesviruses.

Dataset Information

Transcription of true late (?2) cytomegalovirus genes requires UL92 function that is conserved among beta- and gammaherpesviruses.

Publications

Transcription of true late (γ2) cytomegalovirus genes requires UL92 function that is conserved among beta- and gammaherpesviruses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets