Discovery and Characterization of the 1918 Pandemic Influenza Virus in Historical Context

Abstract

The 2005 completion of the entire genome sequence of the 1918 H1N1 pandemic influenza virus represents both a beginning and an end. Investigators have already begun to study the virus in vitro and in vivo to better understand its properties, pathogenicity, transmissibility and elicitation of host responses. Although this is an exciting new beginning, characterization of the 1918 virus also represents the culmination of over a century of scientific research aiming to understand the causes of pandemic influenza. In this brief review we attempt to place in historical context the identification and sequencing of the 1918 virus, including the alleged discovery of a bacterial cause of influenza during the 1889–1893 pandemic, the controversial detection of ‘filter-passing agents’ during the 1918–1919 pandemic, and subsequent breakthroughs in the 1930s that led to isolation of human and swine influenza viruses, greatly influencing the development of modern virology.

Comparison of CpG- and UpA-mediated restriction of RNA virus replication in mammalian and avian cells and investigation of potential ZAP-mediated shaping of host transcriptome compositions

“…Ducks are regarded as the primary reservoir of IAV worldwide, although the virus will transmit readily to other avian species and to mammals. Adaptation to a new host, such as the H1N1 serotype in human following its pandemic spread from 1918 ( Taubenberger et al 2007 ) has been proposed to drive reductions of CpG dinucleotide frequencies ( Greenbaum et al 2008 , 2009a ) potentially associated with a more active ZAP-mediated recognition of avian-adapted viruses ( Gonçalves-Carneiro et al 2021 ). To investigate whether differences in ZAP function in ducks, chickens and mammalian cells led to systematic differences of CpG and UpA representation, we analyzed dinucleotide compositions in a large data set of representative isolates of IAV with annotated hosts from the Influenza Research Database (mammalian: 2949 isolates, primarily H1N1 and H3N2 serotypes; avian: 6417 isolates; Supplemental Data Tables S14, S15 ).…”

“…While superficially attractive as an explanation for the pathogenicity of recently transmitted flu strains, such as those with H5 and H7 HA segments ( Lycett et al 2019 ), the whole framework might be challenged on several grounds. Firstly, the sequence of the 1918 strain was untypical of avian strains generally, and it has been questioned whether the source of the 1918 pandemic strain was actually avian ( Taubenberger et al 2007 ). Secondly, the hypothesis for CpG compositional differences arising from different host selection pressures is inconsistent with the finding of no systematic compositional difference between IAV strains recovered from human and ducks (which show CpG-associated restriction) and chickens (that do not restrict) using linear regression that accommodates the effects of G + C content on CpG composition ( Fig.…”

The 1918–20 Influenza Pandemic

“…However, this task proved to be more complex than was expected because tools to study its genome sequence (structure) were still in their infancy (Bernet & Clark, 1942). It was four decades later (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) that the viral gene was fully sequenced from ribonucleic acid (RNA) fragments of the 1918 pandemic virus and the latter was reconstructed as a fully infectious virus and studied experimentally by a team of US epidemiologists (Anne Reid, T. G. Fanning, John Hultin, J. Taubenberger, Pater Palese, and Adolfor Garcia-Sastre) (Jordan, 2020;Taubenberger et al, 2007). Subsequent research revealed that viral decedents of the 1918 'founder virus' are still circulating today as seasonal influenza A viruses, and subsequent pandemics in 1957, 1968, and 2009 were all caused by genetic updating of the 1918 virus (Taubenberger & Morens, 2020).…”

History repeats itself: the relevance of the 1918 influenza pandemic to the medical school curriculum

“…The spectre of pandemics has long haunted epidemiologists, with an ever-increasing population density, the ability to travel and climate change, leading to concerns about rapid and wide transmissionsconcerns that have been born out in the present coronavirus pandemic. On the other hand, advances in technology since the 1918 H1N1 In uenza pandemic have allowed us to learn more about the pathophysiology, epidemiology, and potential treatment options of viruses such as H1N1 In uenza (4,5).…”

“…Nevertheless, the adage 'history repeats itself' has consistently proved its correctness. The present coronavirus pandemic led people to turn to previous pandemics for guidance (5,6). Indeed, the Covid-19 pandemic and 1918 in uenza pandemic follow similar epidemiologic curves (7).…”