Health & Medical Infectious Diseases

Genomic Signatures of Human versus Avian Influenza A Viruses

Genomic Signatures of Human versus Avian Influenza A Viruses

Abstract and Introduction


Position-specific entropy profiles created from scanning 306 human and 95 avian influenza A viral genomes showed that 228 of 4,591 amino acid residues yielded significant differences between these 2 viruses. We subsequently used 15,785 protein sequences from the National Center for Biotechnology Information (NCBI) to assess the robustness of these signatures and obtained 52 "species-associated" positions. Specific mutations on those points may enable an avian influenza virus to become a human virus. Many of these signatures are found in NP, PA, and PB2 genes (viral ribonucleoproteins [RNPs]) and are mostly located in the functional domains related to RNP-RNP interactions that are important for viral replication. Upon inspecting 21 human-isolated avian influenza viral genomes from NCBI, we found 19 that exhibited ≥1 species-associated residue changes; 7 of them contained ≥2 substitutions. Histograms based on pairwise sequence comparison showed that NP disjointed most between human and avian influenza viruses, followed by PA and PB2.


Pandemic influenza A virus infections have occurred 3 times during the past century; the 1957 (H2N2) and 1968 (H3N2) pandemic strains emerged from a reassortment of human and avian viruses. Recently, all 8 genome segments from the 1918 (H1N1) influenza A virus were completely sequenced. The results indicate that the 1918 pandemic virus may not have emerged by a reassortment of avian and human virus as did the 2 other pandemic strains. Although the 1918 H1N1 is not considered an avian virus, it is the most avianlike of all mammalian influenza viruses. The recent circulation of highly pathogenic avian H5N1 viruses in Asia from 2003 to 2006 has caused ≥90 human deaths and has raised concern about a new pandemic. Therefore, we need to understand what genetic variations could render avian influenza virus capable of becoming a pandemic strain. Genomewide comparison of human versus avian influenza A viruses would show the evolutionary similarities and differences between them and thus provide information for studying the mechanism of influenza viral infection and replication in different host species.

Although many research efforts have focused on the molecular evolution of specific genes of influenza viruses, comprehensive comparisons among the nucleotide sequences of all 8 genomic segments and among the 11 encoded protein sequences have not been extensively reported. In this study, we used several computational approaches for finding specific genetic signatures characteristic of human and avian influenza A viral genomes. We subsequently validated the robustness of those signatures with human and avian protein sequences downloaded from Influenza Virus Resources at the National Center for Biotechnology Information (NCBI) (

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