Topology analysis and visualization of Potyvirus protein-protein interaction network

BackgroundOne of the central interests of Virology is the identification of host factors that contribute to virus infection. Despite tremendous efforts, the list of factors identified remains limited. With omics techniques, the focus has changed from identifying and thoroughly characterizing individual host factors to the simultaneous analysis of thousands of interactions, framing them on the context of protein-protein interaction networks and of transcriptional regulatory networks. This new perspective is allowing the identification of direct and indirect viral targets. Such information is available for several members of the Potyviridae family, one of the largest and more important families of plant viruses.ResultsAfter collecting information on virus protein-protein interactions from different potyviruses, we have processed it and used it for inferring a protein-protein interaction network. All proteins are connected into a single network component. Some proteins show a high degree and are highly connected while others are much less connected, with the network showing a significant degree of dissortativeness. We have attempted to integrate this virus protein-protein interaction network into the largest protein-protein interaction network of Arabidopsis thaliana, a susceptible laboratory host. To make the interpretation of data and results easier, we have developed a new approach for visualizing and analyzing the dynamic spread on the host network of the local perturbations induced by viral proteins. We found that local perturbations can reach the entire host protein-protein interaction network, although the efficiency of this spread depends on the particular viral proteins. By comparing the spread dynamics among viral proteins, we found that some proteins spread their effects fast and efficiently by attacking hubs in the host network while other proteins exert more local effects.ConclusionsOur findings confirm that potyvirus protein-protein interaction networks are highly connected, with some proteins playing the role of hubs. Several topological parameters depend linearly on the protein degree. Some viral proteins focus their effect in only host hubs while others diversify its effect among several proteins at the first step. Future new data will help to refine our model and to improve our predictions.

[1]  Jonathan D. G. Jones,et al.  Evidence for Network Evolution in an Arabidopsis Interactome Map , 2011, Science.

[2]  S. Elena,et al.  A Meta-Analysis Reveals the Commonalities and Differences in Arabidopsis thaliana Response to Different Viral Pathogens , 2012, PloS one.

[3]  J. Riechmann,et al.  Highlights and prospects of potyvirus molecular biology. , 1992, The Journal of general virology.

[4]  Albert-László Barabási,et al.  Statistical mechanics of complex networks , 2001, ArXiv.

[5]  Liying Sun,et al.  Mapping the self-interacting domains of TuMV HC-Pro and the subcellular localization of the protein , 2011, Virus Genes.

[6]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[7]  Kook Hyung Kim,et al.  A protein interaction map of soybean mosaic virus strain G7H based on the yeast two-hybrid system. , 2004, Molecules and cells.

[8]  Piet Van Mieghem,et al.  Topology of molecular interaction networks , 2013, BMC Systems Biology.

[9]  Yutaka Kodama,et al.  An improved bimolecular fluorescence complementation assay with a high signal-to-noise ratio. , 2010, BioTechniques.

[10]  Teresa M. Przytycka,et al.  Chapter 5: Network Biology Approach to Complex Diseases , 2012, PLoS Comput. Biol..

[11]  S. Elena,et al.  Towards an integrated molecular model of plant-virus interactions. , 2012, Current opinion in virology.

[12]  A. Haenni,et al.  Potyvirus proteins: a wealth of functions. , 2001, Virus research.

[13]  Nataša Pržulj,et al.  Protein‐protein interactions: Making sense of networks via graph‐theoretic modeling , 2011, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  Robert E. Rhoads,et al.  The nucleotide sequence of tobacco vein mottling virus RNA , 1986, Nucleic Acids Res..

[15]  S. Fields,et al.  A novel genetic system to detect protein–protein interactions , 1989, Nature.

[16]  J. Culver,et al.  Virus-induced disease: altering host physiology one interaction at a time. , 2007, Annual review of phytopathology.

[17]  Uwe Schlattner,et al.  Yeast Two-Hybrid, a Powerful Tool for Systems Biology , 2009, International journal of molecular sciences.

[18]  R. Russell,et al.  Targeting and tinkering with interaction networks. , 2008, Nature chemical biology.

[19]  M. J. Adams,et al.  Protein-protein interactions in two potyviruses using the yeast two-hybrid system. , 2009, Virus research.

[20]  W. Shen,et al.  Protein interaction matrix of Papaya ringspot virus type P based on a yeast two-hybrid system. , 2010, Acta virologica.

[21]  François Fouss,et al.  An experimental investigation of kernels on graphs for collaborative recommendation and semisupervised classification , 2012, Neural Networks.

[22]  Sourav Bandyopadhyay,et al.  Evolutionarily Conserved Herpesviral Protein Interaction Networks , 2009, PLoS pathogens.

[23]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[24]  Andrew E Firth,et al.  An overlapping essential gene in the Potyviridae , 2008, Proceedings of the National Academy of Sciences.

[25]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Javier De Las Rivas,et al.  Protein–Protein Interactions Essentials: Key Concepts to Building and Analyzing Interactome Networks , 2010, PLoS Comput. Biol..

[27]  K. Nakahara,et al.  The central and C-terminal domains of VPg of Clover yellow vein virus are important for VPg-HCPro and VPg-VPg interactions. , 2003, The Journal of general virology.

[28]  R. Johnston,et al.  The nucleotide sequence of the coding region of tobacco etch virus genomic RNA: evidence for the synthesis of a single polyprotein. , 1986, Virology.

[29]  C. Ward,et al.  Taxonomy of potyviruses: current problems and some solutions. , 1991, Intervirology.

[30]  Chang‐Deng Hu,et al.  Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. , 2002, Molecular cell.

[31]  F. Beaudoin,et al.  Overview and analysis of the polyprotein cleavage sites in the family Potyviridae. , 2005, Molecular plant pathology.

[32]  S. Elena,et al.  A systems biology approach to the evolution of plant-virus interactions. , 2011, Current opinion in plant biology.

[33]  Igor Jurisica,et al.  Functional topology in a network of protein interactions , 2004, Bioinform..

[34]  E. Maiss,et al.  Detection of plum pox potyviral protein-protein interactions in planta using an optimized mRFP-based bimolecular fluorescence complementation system. , 2011, The Journal of general virology.

[35]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[36]  B. Berger,et al.  Herpesviral Protein Networks and Their Interaction with the Human Proteome , 2006, Science.

[37]  M. Pellegrini,et al.  Protein Interaction Networks , 2004, Expert review of proteomics.

[38]  S. Fields,et al.  Protein-protein interactions: methods for detection and analysis , 1995, Microbiological reviews.

[39]  Mark E. J. Newman,et al.  The Structure and Function of Complex Networks , 2003, SIAM Rev..

[40]  S. L. Wong,et al.  Towards a proteome-scale map of the human protein–protein interaction network , 2005, Nature.

[41]  S. Simons,et al.  Economic impact of Turnip mosaic virus, Cauliflower mosaic virus and Beet mosaic virus in three Kenyan vegetables , 2007 .

[42]  C. Daub,et al.  BMC Systems Biology , 2007 .

[43]  C. Myers,et al.  Using networks to measure similarity between genes: association index selection , 2013, Nature Methods.

[44]  A. Barabasi,et al.  An empirical framework for binary interactome mapping , 2008, Nature Methods.

[45]  A. Maule,et al.  New Advances in Understanding the Molecular Biology of Plant/Potyvirus Interactions , 1999 .

[46]  Martin Suter,et al.  Small World , 2002 .

[47]  J. Valkonen,et al.  Proteolytic processing of potyviral proteins and polyprotein processing intermediates in insect and plant cells. , 2002, The Journal of general virology.

[48]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[49]  Shilpa Chakravartula,et al.  Complex Networks: Structure and Dynamics , 2014 .

[50]  A. Gibbs,et al.  Potyviruses and the digital revolution. , 2010, Annual review of phytopathology.

[51]  J. Valkonen,et al.  Towards a protein interaction map of potyviruses: protein interaction matrixes of two potyviruses based on the yeast two-hybrid system. , 2001, The Journal of general virology.

[52]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[53]  A. Barabasi,et al.  Functional and topological characterization of protein interaction networks , 2004, Proteomics.

[54]  M E J Newman Assortative mixing in networks. , 2002, Physical review letters.

[55]  K. Kasschau,et al.  Formation of Complexes at Plasmodesmata for Potyvirus Intercellular Movement Is Mediated by the Viral Protein P3N-PIPO , 2010, PLoS pathogens.