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Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets.

ABSTRACT: Influenza A viruses generate an extreme genetic diversity through point mutation and gene segment exchange, resulting in many new strains that emerge from the animal reservoirs, among which was the recent highly pathogenic H5N1 virus. This genetic diversity also endows these viruses with a dynamic adaptability to their habitats, one result being the rapid selection of genomic variants that resist the immune responses of infected hosts. With the possibility of an influenza A pandemic, a critical need is a vaccine that will recognize and protect against any influenza A pathogen. One feasible approach is a vaccine containing conserved immunogenic protein sequences that represent the genotypic diversity of all current and future avian and human influenza viruses as an alternative to current vaccines that address only the known circulating virus strains.Methodologies for large-scale analysis of the evolutionary variability of the influenza A virus proteins recorded in public databases were developed and used to elucidate the amino acid sequence diversity and conservation of 36,343 sequences of the 11 viral proteins of the recorded virus isolates of the past 30 years. Technologies were also applied to identify the conserved amino acid sequences from isolates of the past decade, and to evaluate the predicted human lymphocyte antigen (HLA) supertype-restricted class I and II T-cell epitopes of the conserved sequences. Fifty-five (55) sequences of 9 or more amino acids of the polymerases (PB2, PB1, and PA), nucleoprotein (NP), and matrix 1 (M1) proteins were completely conserved in at least 80%, many in 95 to 100%, of the avian and human influenza A virus isolates despite the marked evolutionary variability of the viruses. Almost all (50) of these conserved sequences contained putative supertype HLA class I or class II epitopes as predicted by 4 peptide-HLA binding algorithms. Additionally, data of the Immune Epitope Database (IEDB) include 29 experimentally identified HLA class I and II T-cell epitopes present in 14 of the conserved sequences.This study of all reported influenza A virus protein sequences, avian and human, has identified 55 highly conserved sequences, most of which are predicted to have immune relevance as T-cell epitopes. This is a necessary first step in the design and analysis of a polyepitope, pan-influenza A vaccine. In addition to the application described herein, these technologies can be applied to other pathogens and to other therapeutic modalities designed to attack DNA, RNA, or protein sequences critical to pathogen function.

SUBMITTER: Heiny AT

PROVIDER: S-EPMC2065905 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets.

Heiny A T AT Miotto Olivo O Srinivasan Kellathur N KN Khan Asif M AM Zhang G L GL Brusic Vladimir V Tan Tin Wee TW August J Thomas JT

PloS one 20071121 11

<h4>Background</h4>Influenza A viruses generate an extreme genetic diversity through point mutation and gene segment exchange, resulting in many new strains that emerge from the animal reservoirs, among which was the recent highly pathogenic H5N1 virus. This genetic diversity also endows these viruses with a dynamic adaptability to their habitats, one result being the rapid selection of genomic variants that resist the immune responses of infected hosts. With the possibility of an influenza A pa ...[more]

PMID: 18030326

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Project description:ABSTRACT Distinct lineages of avian influenza viruses (AIVs) are harbored by spatially segregated birds, yet significant surveillance gaps exist around the globe. Virtually nothing is known from the Antarctic. Using virus culture, molecular analysis, full genome sequencing, and serology of samples from Adélie penguins in Antarctica, we confirmed infection by H11N2 subtype AIVs. Their genetic segments were distinct from all known contemporary influenza viruses, including South American AIVs, suggesting spatial separation from other lineages. Only in the matrix and polymerase acidic gene phylogenies did the Antarctic sequences form a sister relationship to South American AIVs, whereas distant phylogenetic relationships were evident in all other gene segments. Interestingly, their neuraminidase genes formed a distant relationship to all avian and human influenza lineages, and the polymerase basic 1 and polymerase acidic formed a sister relationship to the equine H3N8 influenza virus lineage that emerged during 1963 and whose avian origins were previously unknown. We also estimated that each gene segment had diverged for 49 to 80 years from its most closely related sequences, highlighting a significant gap in our AIV knowledge in the region. We also show that the receptor binding properties of the H11N2 viruses are predominantly avian and that they were unable to replicate efficiently in experimentally inoculated ferrets, suggesting their continuous evolution in avian hosts. These findings add substantially to our understanding of both the ecology and the intra- and intercontinental movement of Antarctic AIVs and highlight the potential risk of an incursion of highly pathogenic AIVs into this fragile environment. IMPORTANCE Avian influenza viruses (AIVs) are typically maintained and spread by migratory birds, resulting in the existence of distinctly different viruses around the world. However, AIVs have not previously been detected in Antarctica. In this study, we characterized H11N2 viruses sampled from Adélie penguins from two geographically different sites in Antarctica and show that the segmented AIV genome diverged between 49 and 80 years ago from other AIVs, with several genes showing similarity and shared ancestry with H3N8 equine influenza viruses. This study provides the first insight into the ecology of AIVs in Antarctica and highlights the potential risk of an introduction of highly pathogenic AIVs into the continent.

Dataset Information

Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets.

Publications

Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets.

Similar Datasets

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