title: Murine cytomegalovirus protein pM92 is a conserved regulator of viral late gene expression.
abstract: In this study, we report that murine cytomegalovirus (MCMV) protein pM92 regulates viral late gene expression during virus infection. Previously, we have shown that MCMV protein pM79 and its human cytomegalovirus (HCMV) homologue pUL79 are required for late viral gene transcription. Identification of additional factors involved is critical to dissecting the mechanism of this regulation. We show here that pM92 accumulated abundantly at late times of infection in a DNA synthesis-dependent manner and localized to nuclear viral replication compartments. To investigate the role of pM92, we constructed a recombinant virus SMin92, in which pM92 expression was disrupted by an insertional/frameshift mutation. During infection, SMin92 accumulated representative viral immediate-early gene products, early gene products, and viral DNA sufficiently but had severe reduction in the accumulation of late gene products and was thus unable to produce infectious progeny. Coimmunoprecipitation and mass spectrometry analysis revealed an interaction between pM92 and pM79, as well as between their HCMV homologues pUL92 and pUL79. Importantly, we showed that the growth defect of pUL92-deficient HCMV could be rescued in trans by pM92. This study indicates that pM92 is an additional viral regulator of late gene expression, that these regulators (represented by pM92 and pM79) may need to complex with each other for their activity, and that pM92 and pUL92 share a conserved function in CMV infection. pM92 represents a potential new target for therapeutic intervention in CMV disease, and a gateway into studying a largely uncharted viral process that is critical to the viral life cycle.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Chapa
authors.forename: Yi-Cheih
authors.initials: YC
authors.lastname: Perng
authors.forename: Anthony R
authors.initials: AR
authors.lastname: French
authors.forename: Dong
authors.initials: D
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial; D003587:Cytomegalovirus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D017931:DNA Primers; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D014764:Viral Proteins