Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks

Uzoma, Ijeoma; Zhu, Heng

The human a, b, and c herpesviruses cause diseases distinct from one another, ranging from mild cold sores to pneumonitis, birth defects and cancers [35] . Although the viruses are different, once they enter the host cells they all must reprogram cellular gene expression, sense cell-cycle phase, modify cell-cycle progression and reactivate the lytic life cycle to produce new virions to spread infection [37] . Many lytic cycle genes involved in replication of the viral genomes are highly conserved across the herpesvirus family. For example, each herpesvirus encodes for an orthologous serine/threonine kinase [38] that shares structural similarity with human cyclin-dependent kinases (CDKs) [39] and phosphorylates the substrates of CDKs [38] . The ability of viral kinase to mimic host CDKs results in hijacking of key pathways to potentiate their own replication. Particular cellular phosphorylation events are observed during herpes infection and specific phosphorylation of antiviral drugs in infected cells are mediated by the conserved viral kinases [40] . Identifying the collective host targets of the viral kinases would reveal the commonly shared mechanisms and signaling pathways among different herpesviruses to promote their lytic replication. This knowledge will increase the therapeutic target options necessary for developing pan-antivirals.