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Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus.
Nature 2004; 431(7009):703-7Nat

Abstract

The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.

Authors+Show Affiliations

Department of Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15470432

Citation

Kobasa, Darwyn, et al. "Enhanced Virulence of Influenza a Viruses With the Haemagglutinin of the 1918 Pandemic Virus." Nature, vol. 431, no. 7009, 2004, pp. 703-7.
Kobasa D, Takada A, Shinya K, et al. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature. 2004;431(7009):703-7.
Kobasa, D., Takada, A., Shinya, K., Hatta, M., Halfmann, P., Theriault, S., ... Kawaoka, Y. (2004). Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature, 431(7009), pp. 703-7.
Kobasa D, et al. Enhanced Virulence of Influenza a Viruses With the Haemagglutinin of the 1918 Pandemic Virus. Nature. 2004 Oct 7;431(7009):703-7. PubMed PMID: 15470432.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. AU - Kobasa,Darwyn, AU - Takada,Ayato, AU - Shinya,Kyoko, AU - Hatta,Masato, AU - Halfmann,Peter, AU - Theriault,Steven, AU - Suzuki,Hiroshi, AU - Nishimura,Hidekazu, AU - Mitamura,Keiko, AU - Sugaya,Norio, AU - Usui,Taichi, AU - Murata,Takeomi, AU - Maeda,Yasuko, AU - Watanabe,Shinji, AU - Suresh,M, AU - Suzuki,Takashi, AU - Suzuki,Yasuo, AU - Feldmann,Heinz, AU - Kawaoka,Yoshihiro, PY - 2004/07/28/received PY - 2004/08/10/accepted PY - 2004/10/8/pubmed PY - 2004/10/29/medline PY - 2004/10/8/entrez SP - 703 EP - 7 JF - Nature JO - Nature VL - 431 IS - 7009 N2 - The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/15470432/Enhanced_virulence_of_influenza_A_viruses_with_the_haemagglutinin_of_the_1918_pandemic_virus_ L2 - https://doi.org/10.1038/nature02951 DB - PRIME DP - Unbound Medicine ER -