Global Approaches To Study Protein–Protein Interactions Among Viruses and Hosts

Abstract

While high-throughput protein-protein interaction screens were first published approximately 10 years ago, systematic attempts to map interactions among viruses and hosts started only a few years ago. HIV-human interactions dominate host-pathogen interaction databases (with approximately 2000 interactions) despite the fact that probably none of these interactions have been identified in systematic interaction screens. Recently, combinations of protein interaction data with RNAi and other functional genomics data allowed researchers to model more complex interaction networks. The rapid progress in this area promises a flood of new data in the near future, with clinical applications as soon as structural and functional genomics catches up with next-generation sequencing of human variation and structure-based drug design. Keywordshepatitis C virus; herpes viruses; HIV; mass spectrometry; protein interaction networks; protein purification; RNAi; yeast two-hybrid screens Host-virus interactions have been studied since the discovery of viruses in 1898, when Martinus Beijerinck described tobacco mosaic virus. However, only with the invention of the electron microscope, protein biochemistry and eventually nucleic acid sequencing has their systematic molecular characterization become possible. Considering their small size, it was no surprise that the first completely sequenced genome was a phage, namely MS2 [1]. To date, more than 5000 viruses have been described [2,101], although many have not been completely sequenced nor classified into any of the major virus families. The National Center for Biotechnology Information (NCBI) genome database lists 3398 complete sequences for 2319 viral genomes [102]. In fact, there may be up to a billion virus particles present in a milliliter of seawater, at least in certain areas [3], and most bacteria and higher organisms appear to be infected by phage or other viruses (e.g., [4]). If there are millions of species in our biosphere there is likely to be a similar number of viral species that infect them. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NIH Public Access Experimental methods to study host-pathogen interactionsIn contrast to viruses that enter their host cells completely and must express all their proteins in the host cell, many bacteria inject only a few effector proteins into their host cells. For example, pathogenic Escherichia coli strains such as O157 encode in the order of 50 effector proteins that are injected into host cells [6]. The challenge here is to identify the bacterial effector proteins. For viruses, we can safely assume that all viral proteins enter the cell. Thus, an important goal of virus studies is to analyze the activity of each protein inside the cell. Initially this ca...

Mapping of Chikungunya Virus Interactions with Host Proteins Identified nsP2 as a Highly Connected Viral Component

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