Tumpey, T. M. et al. Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. Proc. Natl Acad. Sci. USA 101, 3166-3171

Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA 30605, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2004; 101(9):3166-71. DOI: 10.1073/pnas.0308391100
Source: PubMed


The 1918 influenza A H1N1 virus caused the worst pandemic of influenza ever recorded. To better understand the pathogenesis and immunity to the 1918 pandemic virus, we generated recombinant influenza viruses possessing two to five genes of the 1918 influenza virus. Recombinant influenza viruses possessing the hemagglutinin (HA), neuraminidase (NA), matrix (M), nonstructural (NS), and nucleoprotein (NP) genes or any recombinant virus possessing both the HA and NA genes of the 1918 influenza virus were highly lethal for mice. Antigenic analysis by hemagglutination inhibition (HI) tests with ferret and chicken H1N1 antisera demonstrated that the 1918 recombinant viruses antigenically most resembled A/Swine/Iowa/30 (Sw/Iowa/30) virus but differed from H1N1 viruses isolated since 1930. HI and virus neutralizing (VN) antibodies to 1918 recombinant and Sw/Iowa/30 viruses in human sera were present among individuals born before or shortly after the 1918 pandemic. Mice that received an intramuscular immunization of the homologous or Sw/Iowa/30-inactivated vaccine developed HI and VN antibodies to the 1918 recombinant virus and were completely protected against lethal challenge. Mice that received A/PR/8/34, A/Texas/36/91, or A/New Caledonia/20/99 H1N1 vaccines displayed partial protection from lethal challenge. In contrast, control-vaccinated mice were not protected against lethal challenge and displayed high virus titers in respiratory tissues. Partial vaccine protection mediated by baculovirus-expressed recombinant HA vaccines suggest common cross-reactive epitopes on the H1 HA. These data suggest a strategy of vaccination that would be effective against a reemergent 1918 or 1918-like virus.

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    • "The HA sequence of A(H1N1)pdm09 was found to be closely related to the current H1 subtype swine viruses, circulating in pigs at least since the 1930s without drifting significantly (Garten et al., 2009; Smith et al., 2009), and related to the human H1N1 that caused the 1918 Spanish influenza pandemic (Masoodi et al., 2012). In contrast, the HAs of human H1N1 viruses causing seasonal outbreaks after 1977 but before 2009 had diverged extensively from the earliest 1918 H1N1 virus (Tumpey et al., 2004). These results can explain the reported presence of antibodies that neutralize pandemic A(H1N1)pdm09 virus in individuals born prior to 1918 but their absence in younger subjects (Hancock et al., 2009; Itoh et al., 2009). "
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    • "Influenza A virus (IAV), a member of the Orthomyxoviridae, contains eight segmented RNA genomes within a viral membrane (1,2). Retrospective studies of the reconstructed 1918 influenza virus revealed that the NS1 (3), hemagglutinin (HA) (4,5), neuraminidase (NA) (6), PB1-F2 (7), and replication complex (PB2, PB1, PA, and NP) (8) proteins determined the high virulence of the 1918 ‘Spanish Flu’ (H1N1). The well-organized genetic network of 1918 H1N1 allowed this virus to efficiently infect humans, and it claimed an estimated 50 million lives. "
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    • "Ancient DNA has also been used to reveal the evolutionary origin of human populations [6-8] and to investigate our relationships with archaic hominins [9-11]. The sequencing of nucleic acids from ancient pathogens, including the 1917 influenza virus responsible for 20–40 millions of human deaths worldwide [12], has provided insights into the molecular mechanisms involved in virulence with potential applications in medicine and epidemiological surveys. "
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