From ORFeomes to Protein Interaction Maps in Viruses

Abstract

Although cloned viral ORFeomes are particularly well suited for genome-wide interaction mapping due to the limited size of viral genomes, only a few such studies have been published. Here, we summarize virus interaction mapping projects involving vaccinia virus, hepatitis C virus (HCV), potato virus A (PVA), pea seed-borne mosaic virus (PSbMV), and bacteriophage T7, as well as some projects in progress. The studies reported suggest that virus-specific coding and replication strategies must be taken into account to yield accurate numbers of protein interactions. In particular, the number of false negatives can be significant for RNA viruses expressing precursor polyproteins (because interactions between full-length mature proteins are often not detected due to incorrect processing) and for viruses replicating in the cytoplasm whose transcripts have not been selected for splicing signals.In conclusion, the studies on viral protein interaction maps suggest that cloned pathogen ORFeomes will contribute to a holistic picture of the pathogenesis of infectious diseases and are ideal starting points for new approaches in systems biology. Both viral ORFeome and interaction mapping projects are being documented on our Web site

Exploration of Panviral Proteome: High-Throughput Cloning and Functional Implications in Virus-host Interactions

“…Viruses have developed a variety of delicate strategies to facilitate their invasion and replication/transcription of their genomes, while at the same time silencing host immune responses by manipulating host proteins and cellular processes. The systematic characterization of the viral proteome-host interactions, and the identification of new host targets, would be invaluable in the understanding of viral invasion and replication mechanisms in infectious diseases, autoimmune diseases, and cancer 2. The findings from these studies will greatly facilitate the detection of viral infection and progression, antiviral drug discovery, and therapeutic treatment 3-5.…”

Defining Viral Protein Interactomes Using the Yeast Two-Hybrid Assay

“…In the case of KSHV, a genome wide Y2H matrix screen identified 125 interactions, out of which only 3 were previously known ( Table 1). In addition, around 50% of the Y2H interactions were confirmed with a co-immunoprecipitation assay (Uetz et al, 2004). A network of interconnecting interactions involving proteins unique to KHSV as well as those conserved across the different herpes viral classes was established.…”

La cellule infectée virtuelle

“…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]. Comme pour les interactomes des organismes modèles, ces avancées ont été rendues possibles par le développement de larges collections d'ORF (open reading frame, cadre ouvert de lecture) ou ORFéome [16,17]. Ainsi, dans le cadre du projet I-MAP (infectious mapping project), le premier ORFéome viral est en cours d'assemblage dans le but de faciliter l'étude systématique des fonctions des protéines virales tout en prenant 2 Biologie systémique et « -omiques », vers un avatar moléculaire de la cellule L'avènement des techniques de séquençage, de criblage de géno-mique fonctionnelle (ARN interférents, criblage de petites molé-cules, etc.)…”