Showing papers by "Vladimir Brusic published in 2009"
TL;DR: A large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences, identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes.
Abstract: West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. We describe a large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. This study, which used 2,746 WNV protein sequences collected from the NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or more, which are immunologically relevant as potential T-cell epitopes. Entropy-based analysis of the diversity of WNV sequences, revealed the presence of numerous evolutionarily stable nonamer positions across the proteome (entropy value of < or = 1). The representation (frequency) of nonamers variant to the predominant peptide at these stable positions was, generally, low (< or = 10% of the WNV sequences analyzed). Eighty-eight fragments of length 9-29 amino acids, representing approximately 34% of the WNV polyprotein length, were identified to be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88 completely conserved sequences, 67 are also present in other flaviviruses, and several have been associated with the functional and structural properties of viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of conserved sequences are potentially immunogenic, while 44 contained experimentally confirmed human T-cell epitopes. This study identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes. The complete conservation of these immunologically relevant sequences through the entire recorded WNV history suggests they will be valuable as components of peptide-specific vaccines or other therapeutic applications, for sequence-specific diagnosis of a wide-range of Flavivirus infections, and for studies of homologous sequences among other flaviviruses.
25 citations
TL;DR: It is suggested that pathogens have evolved under the influence of the host immune system so that surface proteins are depleted in potential MHC-binding peptides, and that identification of a protein likely to contain a single immuno-dominant epitope is likely to be a productive strategy for vaccine design.
8 citations
TL;DR: The data suggest that donor-derived MM-specific adaptive immunity contributes to disease regression following syngeneic HSCT for MM, and PIM1 and DAPK2 are MM-associated antigens that commonly generate processed epitopes on malignant MM cells.
1 citations
15 Oct 2009
TL;DR: The ImmunoGrid project has proved that simulators can be used in conjunction with grid technologies for drug and vaccine discovery, demonstrating that it is possible to drastically reduce the developing time of such products.
Abstract: In this paper we present the ImmunoGrid project, whose goal is to develop an immune system simulator which integrates molecular and system level models with Grid computing resources for large-scale tasks and databases. We introduce the models and the technologies used in the ImmunoGrid Simulator, showing how to use them through the ImmunoGrid web interface. The ImmunoGrid project has proved that simulators can be used in conjunction with grid technologies for drug and vaccine discovery, demonstrating that it is possible to drastically reduce the developing time of such products.