Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI

Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through the assembly of repressive chromatin remodeling complexes targeting incoming viral genomes. However, it has remained unclear how initial transcriptional activation of the adenoviral genome is achieved. Here we show that Daxx mediated repression of the immediate early Ad E1A promoter is efficiently counteracted by the capsid protein VI. This requires a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses were also shown to activate the Ad E1A promoter independent of Ad gene expression and support virus replication. Our results show how Ad entry is connected to transcriptional activation of their genome in the nucleus. Our data further suggest a common principle for genome activation of DNA viruses by counteracting Daxx related repressive mechanisms through virion proteins

PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor-suppressor p53

Although modulation of the cellular tumor-suppressor p53 is considered to have the major role in E1A/E1B-55K-mediated tumorigenesis, other promyelocytic leukemia nuclear body (PML-NB)/PML oncogenic domain (POD)-associated factors including SUMO, Mre11, Daxx, as well as the integrity of these nuclear bodies contribute to the transformation process. However, the biochemical consequences and oncogenic alterations of PML-associated E1B-55K by SUMO-dependent PML-IV and PML-V interaction have so far remained elusive. We performed mutational analysis to define a PML interaction motif within the E1B-55K polypeptide. Our results showed that E1B-55K/PML binding is not required for p53, Mre11 and Daxx interaction. We also observed that E1B-55K lacking subnuclear PML localization because of either PML-IV or PML-V-binding deficiency was no longer capable of mediating E1B-55K-dependent SUMOylation of p53, inhibition of p53-mediated transactivation or efficiently transforming primary rodent cells. These results together with the observation that E1B-55K-dependent SUMOylation of p53 is required for efficient cell transformation, provides evidence for the idea that the SUMO ligase activity of the E1B-55K viral oncoprotein is intimately linked to its growth-promoting oncogenic activities

Interplay between viruses and host sumoylation pathways

Post-translational modification by members of the small ubiquitin-like modifier (SUMO) family of proteins is important for the regulation of many cellular proteins and pathways. As obligate parasites, viruses must engage with the host cell throughout their replication cycles, and it is therefore unsurprising that there are many examples of interplay between viral proteins and the host sumoylation system. This article reviews recent advances in this field, summarizing information on sumoylated viral proteins, the varied ways in which viruses engage with SUMO-related pathways, and the consequences of these interactions for viral replication and engagement with innate and intrinsic immunity

DEVELOPMENT OF PROCESS, SIMULATION OF CONCENTRATION PROCESS OF OXIDIZED IRON AND CHROMIUM ORES IN SUSPENSION HYDROCYCLONES

There the hydrocyclone process has been studied as alternative for the jigging in view to decrease of losses of valuable components in concentration of oxidized iron ores. The study of flow pattern by means of air-buble flares of rate transducers and by means of photography allowed to confirm the existence of high-rate (up to 1,2 m/s) local radial flow in the field of edge of outlet. The separation mechanism in two- and three-product (with coaxial tubes) hydrocyclones has been offered. The optimum relations of lengthes of internal branch pipes and of cylindrical part of hydrocyclone have been ascertained. The factors which provide for maximum of separation density have been recommended on the basis of methods of hydromechanics and mechanics. The simulator of hydrocyclone process (as the set of regression equations) and the calculation procedure of loads of regeneration system and of expectable production indicators of concentration have been developed. The effectiveness of developed concentration process has been checked under the industrial conditions. The developed concentration process of chromium ores has been accepted for use in the Don Ore Mining-and-Processing Enterprise. The study results may by used for design, for prediction estimation of concentrating capacity of ores and in the educational processAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio