Evolutionarily Conserved Herpesviral Protein Interaction Networks

Abstract

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.

Graphics processing unit‐based alignment of protein interaction networks

“…Given two CGOPs, u, j(u) and v, j(v), there is an interaction between u and v. If there is an interaction between j(u) and j(v), Fig. 8 Phylogenetic trees reconstructed using three different methods a Phylogenetic tree reconstructed using the method of Fossum et al [20] b Phylogenetic tree reconstructed using the method of Natasa et al [8] c Phylogenetic tree reconstructed using HGA-2N The three trees show the same phylogenetic relationships these two interactions are conserved interactions. If there is no interaction between j(u) and j(v), a potential interaction can be predicted between j(u) and j(v).…”

La cellule infectée virtuelle

“…Une partie de ces défenses immunitaires est innée et s'exprime très précocement au sein des cellules de l'organisme en réponse à l'activation de sentinelles moléculaires. C'est le cas des récepteurs membranaires TLR (récepteurs Toll-like) et des senseurs intracellulaires l'interactome viral par la technologie du double hybride en levure (Y2H : yeast two-hybrid) réalisées à l'échelle de plusieurs virus entiers dont celui de l'hépatite C [9], du SARS (severe acute respiratory syndrome) [10] et de plusieurs herpèsvirus [11,12]. Des travaux récents ont également été entrepris pour explorer sans a priori l'interactome virus-hôte, dont celui de l'EBV (Epstein Barr [13], du virus de l'hépatite C [14] et du virus de la vaccine [15].…”

Protein networks in diseases

“…Further, on studying three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, a core set of highly conserved protein interactions were identified. Interactions are conserved between orthologous proteins despite low sequence similarity, suggesting that function may be more conserved than the sequence [7]. While another study revealed, the inducible form of cyclooxygenase is COX-2 expression, whose tight regulation is necessary for controlling eicosanoid production in atherosclerosis and other inflammatory syndromes.…”