The study by Taubenberger et al. (2005) investigates the polymerase genes of the 1918 influenza virus, which caused a global pandemic in 1918-1919. The polymerase complex consists of PA, PB1, and PB2 proteins, which are crucial for viral replication and host specificity. The 1918 virus's polymerase genes differ from avian sequences by only a few amino acids, suggesting they originated from an avian source shortly before the pandemic. However, the nucleotide sequences show more synonymous differences than expected, indicating evolutionary distance from known avian strains. Phylogenetic analyses and sequence comparisons reveal that the 1918 virus was likely an entirely avian-like virus that adapted to humans, rather than a reassortant virus like those of the 1957 and 1968 pandemics. Ten amino acid changes in the polymerase proteins consistently differentiate the 1918 virus from subsequent human influenza viruses, and some of these changes are also found in highly pathogenic H5N1 viruses that have caused human illness and death. These findings suggest that the 1918 virus's adaptation to humans involved specific genetic changes that facilitated virus replication and increased pathogenicity.The study by Taubenberger et al. (2005) investigates the polymerase genes of the 1918 influenza virus, which caused a global pandemic in 1918-1919. The polymerase complex consists of PA, PB1, and PB2 proteins, which are crucial for viral replication and host specificity. The 1918 virus's polymerase genes differ from avian sequences by only a few amino acids, suggesting they originated from an avian source shortly before the pandemic. However, the nucleotide sequences show more synonymous differences than expected, indicating evolutionary distance from known avian strains. Phylogenetic analyses and sequence comparisons reveal that the 1918 virus was likely an entirely avian-like virus that adapted to humans, rather than a reassortant virus like those of the 1957 and 1968 pandemics. Ten amino acid changes in the polymerase proteins consistently differentiate the 1918 virus from subsequent human influenza viruses, and some of these changes are also found in highly pathogenic H5N1 viruses that have caused human illness and death. These findings suggest that the 1918 virus's adaptation to humans involved specific genetic changes that facilitated virus replication and increased pathogenicity.