H1N1-influenza as Lazarus: Genomic resurrection from the tomb of an unknown
Joshua LederbergAuthors Info & Affiliations
February 27, 2001
98 (5) 2115-2116
https://doi.org/10.1073/pnas.051000798
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The 1918–1919 pandemic of H1N1 virus influenza was the greatest acute plague of the 20th century. Incurring over 20 million human fatalities, however, was not a good strategy for sustaining the evolutionary fitness of the virus, because it is no longer extant; whereas, say, measles and chickenpox remain with us with no evidence of remarkable genetic change, although this may become more evident if they were to face total or near eradication through vaccination programs. The folly of flu virulence remains our chagrin, because the threat always looms over us that this family of viruses, endemic in birds, again may generate human-lethal gene reassortments. We had valid scares about that contingency with the appearance of H5N1 variant flu in Hong Kong just 3 years ago. Influenza can be regarded as a zoonosis prevalent in birds, many of them world travelers, with occasional outbreaks in humans and other animals mainly rooted in nature's own experiments in genetic engineering. Special importance is attached to reassortments between bird- and human-adapted strains most likely to occur in habitats with close contact between birds, e.g., ducks, humans, and swine (as a mixing reservoir; ref. 1). For these reasons, high urgency attaches to efforts to resurrect genetic information about the singularities of H1N1–1918. The intact virus is nowhere to be found, but genomic fragments can still be detected sensitively and diagnosed. Exemplifying the latest technical advances in the use of DNA amplification, reverse-transcriptase–PCR (RT-PCR), Jeffery Taubenberger and his associates at the Armed Forces Institute of Pathology initiated the tour de force of recovering sequences of flu from paraffin-embedded pathological specimens preserved since 1918 in the AFIP collections (2). These sources then were augmented by samples from frozen remains of an Inuit woman who succumbed to the flu in 1918 and was buried in permafrost at Brevig Mission on the Seward Peninsula of Alaska's western coast, not far from the Bering Strait. This nameless woman has left an indelible mark on world medical history (3). Now, as reported in this issue, the AFIP team has joined forces with teams from the U.S. Department of Agriculture and the Peter Palese/Adolfo García-Sastre groups at Mt. Sinai Medical School in a further quest for the RNA sequences of H1N1–1918 that might account for its historic human virulence (4).
Previous work has focused on two well studied gene products: hemagglutinin (HA) and neuraminidase (NA), which dominate the surface specificities of the virus and underlie most of its taxonomy (e.g., H1N1 refers to type 1 hemagglutinin, type 1 neuraminidase). These gene products are also the chief determinants of specificity in vaccine prophylaxis for flu strains circulating at any given time. HA variation can account for fluctuations of virulence and host specificity of extant flu viruses. However, nothing remarkable was seen in the HA or the NA of H1N1–1918.
https://www.pnas.org/doi/full/10.1073/pnas.051000798
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