Evolutionarily Conserved Herpesviral Protein Interaction Networks

Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species

Protein-protein Interaction Networks of E. coli and S. cerevisiae are similar

Only recently novel high-throughput binary interaction data in E. coli became available that allowed us to compare experimentally obtained protein-protein interaction networks of prokaryotes and eukaryotes (i.e. E. coli and S. cerevisiae). Utilizing binary-Y2H, co-complex and binary literature curated interaction sets in both organisms we found that characteristics of interaction sets that were determined with the same experimental methods were strikingly similar. While essentiality is frequently considered a question of a protein's increasing number of interactions, we found that binary-Y2H interactions failed to show such a trend in both organisms. Furthermore, essential genes are enriched in protein complexes in both organisms. In turn, binary-Y2H interactions hold more bottleneck interactions than co-complex interactions while both binary-Y2H and co-complex interactions are strongly enriched among co-regulated proteins and transcription factors. We discuss if such similarities are a consequence of the underlying methodology or rather reflect truly different biological patterns