Characterization of the 1918 influenza virus polymerase genes

  title={Characterization of the 1918 influenza virus polymerase genes},
  author={Jeffery K. Taubenberger and Ann H. Reid and Raina M. Lourens and Ruixue Wang and Guozhong Jin and Thomas G. Fanning},
The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors, thereby having a role in host specificity. The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian… 
Origin of the 1918 pandemic H1N1 influenza A virus as studied by codon usage patterns and phylogenetic analysis.
A broad genetic and phylogenetic analysis of a wide range of influenza virus genes, in particular the PB1 gene, to gain information about the phylogenetic relatedness of the 1918 H1N1 virus found the high stability of the RSCU pattern of thePB1 gene indicated that the integrity of RNA structure is more important for influenza virus evolution than previously thought.
Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes
Comparing genomics with the human and avian versions of the H1N1 influenza virus finds that the nucleotide compositions of influenza A viruses infecting the two hosts are sufficiently different that the host is determined at almost 100% accuracy.
The origin and virulence of the 1918 "Spanish" influenza virus.
  • J. Taubenberger
  • Biology, Medicine
    Proceedings of the American Philosophical Society
  • 2006
Sequence and phylogenetic analysis of the completed 1918 influenza virus genes shows them to be the most avian-like among the mammalian-adapted viruses, which supports the hypotheses that (1) the pandemic virus contains genes derived from avan-like influenza virus strains and (2) the 1918 virus is the common ancestor of human and classical swine H1N1 influenza viruses.
Analysis by Single-Gene Reassortment Demonstrates that the 1918 Influenza Virus Is Functionally Compatible with a Low-Pathogenicity Avian Influenza Virus in Mice
Data suggest that the 1918 virus, whatever its origin, is very similar to avian influenza virus, and the mechanisms of influenza virus host switch, and particularly mammalian host adaptation are still only partly understood.
Acquisition of Avian-Origin PB1 Facilitates Viral RNA Synthesis by the 2009 Pandemic H1N1 Virus Polymerase
Using the 2009 pandemic H1N1 virus as a model, it is demonstrated that the acquisition of an avian PB1 markedly enhances viral RNA synthesis of the2009 pandemic virus polymerase, providing the first insight into the mechanism via which avian-origin PB1 enhances viral transcripts synthesis.
Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses
H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses.
Adaptive strategies of the influenza virus polymerase for replication in humans
A strategy used by the 2009 H1N1 influenza A virus to acquire second-site suppressor mutations in its PB2 polymerase subunit is revealed and other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans are identified.
Reassortment and Mutation of the Avian Influenza Virus Polymerase PA Subunit Overcome Species Barriers
The data suggest that the human, avian, swine, and 2009 H1N1-like viruses that are currently cocirculating in pig populations set the stage for PA reassortments with the potential to generate novel viruses that could possess expanded tropism and enhanced pathogenicity.
Influenza A Virus Polymerase Is a Site for Adaptive Changes during Experimental Evolution in Bat Cells
The results demonstrate that bats are unique hosts that select for both a novel mutation and a well-known adaptive mutation in the viral polymerase to support replication, and suggest that replication of human influenza A viruses in a nonnative host drives the evolution of new variants and may be an important source of genetic diversity.
Evidence for Avian and Human Host Cell Factors That Affect the Activity of Influenza Virus Polymerase
It is suggested that the well-known adaptative mutation E627K on viral protein PB2 facilitates the ability of a human positive factor to enhance replication of influenza virus in human cells.


Novel Origin of the 1918 Pandemic Influenza Virus Nucleoprotein Gene
The results are consistent with the existence of a currently unknown host for influenza, with an NP similar to current avian strain NPs at the amino acid level but with many synonymous nucleotide differences, suggesting evolutionary isolation from the currently characterized avian influenza virus gene pool.
Characterization of the 1918 “Spanish” Influenza Virus Matrix Gene Segment
The 1918 sequence matches other mammalian strains at 4 amino acids in the extracellular domain of M2 that differ consistently between avian and mammalian strains, suggesting that the matrix segment may have been circulating in human strains for at least several years before 1918.
Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes
The sequence of the A/Brevig Mission/1/18 (H1N1) virus nonstructural (NS) segment encoding two proteins, NS1 and nuclear export protein is reported, suggesting that interaction of the NS1 protein with host-cell factors plays a significant role in viral pathogenesis.
Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus
It is demonstrated that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host.
Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses.
The results showed that replication of the viral-like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins.
Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics.
Comparative analysis of deduced amino acid sequences disclosed highly conserved regions in PB1 proteins, which may be key structures required for PB1 activities.
Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand.
The Thailand viruses contained more avian-specific residues than the 1997 Hong Kong H5N1 viruses, suggesting that the virus may have adapted to allow a more efficient spread in avian species.
Characterization of the 1918 "Spanish" influenza virus neuraminidase gene.
The complete coding sequence of the neuraminidase gene of the 1918 virus is determined and appears to be intermediate between mammals and birds, suggesting that it was introduced into mammals just before the 1918 pandemic.
Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus
Analyses of the genes of the 1918 pandemic virus indicate that this strain might have had a different origin, and whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.
A single amino acid in the PB2 gene of influenza A virus is a determinant of host range
The nucleotide sequences of thePB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu-->Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells.