Developmental Milestones/Developments to Date:
Current Assessment/State of the Field:
Taubenberger, Jeffery K., et. al., “Characterization of the 1918 influenza virus polymerase genes,” Nature Publishing Group, vol. 437. October 6, 2005, pg. 889-893. http://apps.isiknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=2&SID=2EiKADk7afodFK7dgKI&page=3&doc=21 and http://www.nature.com/nature/journal/v437/n7060/full/nature04230.html
- “Unlike the 1957 and 1968 pandemics, however, the 1918 virus was mostly not a human/ avian reassortant virus, but rather an avian-like virus that adapted to humans ”in toto”.”
- “only a small number of amino acids, consistent with the hypothesis that they were derived from an avain source.” p.889
- “Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus and propose that the 1918 virus was not a reassortant virus but more likely an entirely avian-like virus that adapted to humans.” p.889 *”resulted in the death of approximately 50 million people.” p.889
- “A single amino acid change in PB2, E627k, was shown (1) to be important for mammalian adaptation, (2) to distinguish highly pathogenic avian influenza (HPAI) H5N1 viruses in mice, and (3) to be present in the single fatal human infection during he HPAI H7N7 outbreak in the Netherland in 2003 (ref. 20), and in some recent H5N1 isolates from humans in Vietnam and Thailand and wild birds in china.” p.889
- “there are only 10 amino acid positions (out of 2,232 total codons) that consistently distinguish the 1918 and subsequent human polymerase proteins PB2, PB1, and PA from their avian influenza counterparts.” p. 890
- “In the PB2 protein, five changes distinguish the human isolates from avian sequences.” p.890
- “Perhaps most interestingly, the 1918 virus and subsequent human isolates have a Lys residue at position 627. This residue has been implicated in host adaptation, and has previously been shown to be crucial for high pathogenicity in mice infected with the 1997 H5N1 virus.” p.891
- “The PA protein shows a similar pattern: four residues consistently differ between 1918 and subsequent human isolates and the avian consensus sequence.” p.891
- “Human H1N1, H2N2 and H3N2 viruses derived from the 1918, 1957 and 1968 pandemics, respectively, each possessed a uniquely derived avian-like PB1 gene segment, and so we sought to identify any parallel changes that might shed light on human adaptation.” p.892
- “The three human pandemic PB1 proteins differ from the avian consensus by only 4-7 residues each (Supplementary Fig. 2). Only one of these changes is shared among the pandemic isolates: N375S change.” p 892
- “The data presented here highlight the marked conservation of the PB1 protein in avian influenza viruses. PB1 functions as an RNA-dependent RNA polymerase, and so it is reasonable to hypothesize that its enzymatic function is optimal in the conserved form.” p892
- “Supporting this hypothesis, a recent study examining combinations of avin and human influenzapolymerases showed that the most efficient influenza transcriptional activity ”in vitro” was seen with an avian-derived PB1, even if the PB2, PA and NP proteins were from a human virus. Acquiring an avian P1 by reassortment might provide a replicative advantage to the new virus, possibly explaining why both of the last two pandemics and the 1918 influenza virus all had very avian-like PB1 proteins.” p. 892
- (LOOK AT METHODS SECTION ON P. 892)
- ”Note: This article has been cited 246 times as of October 5, 2009 as recorded by the Web of Science”.
Kaiser, Jocelyn, “Resurrected Influenza Virus Yields Secrets of Deadly 1918 Pandemic”, Science, Vol. 310, 7 October 2005, page 28-29.
- “The research grows out of Armed Forces Institute of Pathology (AFIP) pathologist Jeffery Taubenberger’s efforts, begun in 1995, to sequence the genome of the 1918 flu virus. Working mainly with tissue from a victim found in permafrost in Alaska, he and others have been piecing together the virus’s eight genes and characterizing their protein products.”
- “Because of the sensitive nature of the work, the Centers for Disease Control and Prevention (CDC) lab’s safety precautions received unusual scrutiny, says Tumpey, including review by several biosafety committees. Workers followed biosafety level 3 (BSL-3) practices, with additional enhancements for instance, wearing battery-powered air purifiers with face shields and showering when leaving the lab.”
- “A new federal biosecurity board gave the paper an unusual last-minute review to make sure the merits of its publication outweighed the risks of releasing potentially dangerous knowledge. The board’s green light is a relief to scientists who have worried about a clampdown on scientific information following the anthrax attacks.” *“Science decided to publish the 1918 flu paper because it ‘could help prevent another global flu pandemic,’ says Editor-in-Chief Donald Kennedy.”
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