Viral proteomics: The emerging cutting-edge of virus research

Zhou, ShengTao; Liu, Rui; Zhao, Xia; Huang, CanHua; Wei, YuQuan

The previously described technologies only offer a descriptive view of protein-protein interactions. They cannot characterize the physiological significance of these interactions, which are often elucidated by mutations or other functional experiments. In recent years, the development of RNAibased methods for protein knockdown in mammalian cells has allowed unparalleled flexibility in the study of protein function. Large siRNA libraries are now available that allow the knockdown of all proteins known to be encoded by the human genome. These libraries have been used to provide mechanistic explanations by depleting RNAs of defined genes. Together with bioinformatics analysis, this approach has played a pivotal role in identifying host factors required for such viruses as HIV, flaviviruses, and the H1N1 virus. Thus, RNAi screens and protein interaction screens perfectly complement protein-protein interaction screens [45] . For example, Brass et al. [46] and Konig et al. [47] conducted two independent investigations that systematically screened for human genes indispensable for HIV infection and replication. They identified 284 and 295 required cell factors, respectively, with an overlap of 13 genes. Integration of RNAi data and protein interaction data generated a host-pathogen interaction network comprising 213 functionally validated and 169 predicted HIV host cellular nodes. These nodes were cross-linked via 2291 binary protein interactions and 318 interactions to HIV-encoded proteins. This RNAi analysis revealed the biological context through phenotypes provided simultaneous mechanistic explanations for these phenotypes.