Abstract
BackgroundHost protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. The resulting network topology favors excessive amounts of virus production in a stressed host cell network. Short linear peptide motifs common to both virus and host provide the basis for host network modification.MethodsWe focused our host-pathogen study on the binding and competing interactions of HIV-1 and human proteins. We showed that peptide motifs conserved across 70% of HIV-1 subtype B and C samples occurred in similar positions on HIV-1 proteins, and we documented protein domains that interact with these conserved motifs. We predicted which human proteins may be targeted by HIV-1 by taking pairs of human proteins that may interact via a motif conserved in HIV-1 and the corresponding interacting protein domain.ResultsOur predictions were enriched with host proteins known to interact with HIV-1 proteins ENV, NEF, and TAT (p-value < 4.26E-21). Cellular pathways statistically enriched for our predictions include the T cell receptor signaling, natural killer cell mediated cytotoxicity, cell cycle, and apoptosis pathways. Gene Ontology molecular function level 5 categories enriched with both predicted and confirmed HIV-1 targeted proteins included categories associated with phosphorylation events and adenyl ribonucleotide binding.ConclusionA list of host proteins highly enriched with those targeted by HIV-1 proteins can be obtained by searching for host protein motifs along virus protein sequences. The resulting set of host proteins predicted to be targeted by virus proteins will become more accurate with better annotations of motifs and domains. Nevertheless, our study validates the role of linear binding motifs shared by virus and host proteins as an important part of the crosstalk between virus and host.
Highlights
Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others
We focus on protein interactions mediated by short eukaryotic linear motifs (ELMs) [11] on HIV-1 proteins and human protein counter domains (CDs) known to interact with these ELMs
We looked at all interactions documented in Human Protein Reference Database (HPRD) that could be explained by an interaction between a virus protein's conserved ELM and a CD known to interact with that ELM, and added the protein with the CD to H1 and the protein with the ELM to H2
Summary
Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. Previous host-pathogen interaction prediction methods focused largely on finding PPIs between human and cellular parasite proteins. One recent method found the probability that two protein domains interact given the human PPI network, and used this probability to find the likelihood that pathogen and human proteins interact given their domain profiles [8]. Another method matched human and pathogen protein pairs to proteins known to form complexes, and filtered these interaction candidates based on expression data from human and pathogen [9]. To find structures for the N-terminal and C-terminal domains of HIV-1 VIF, two different protein structures were required for comparative modeling [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
