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Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus.
Proc Natl Acad Sci U S A 2002; 99(21):13849-54PN

Abstract

The 1918 influenza pandemic caused more than 20 million deaths worldwide. Thus, the potential impact of a re-emergent 1918 or 1918-like influenza virus, whether through natural means or as a result of bioterrorism, is of significant concern. The genetic determinants of the virulence of the 1918 virus have not been defined yet, nor have specific clinical prophylaxis and/or treatment interventions that would be effective against a re-emergent 1918 or 1918-like virus been identified. Based on the reported nucleotide sequences, we have reconstructed the hemagglutinin (HA), neuraminidase (NA), and matrix (M) genes of the 1918 virus. Under biosafety level 3 (agricultural) conditions, we have generated recombinant influenza viruses bearing the 1918 HA, NA, or M segments. Strikingly, recombinant viruses possessing both the 1918 HA and 1918 NA were virulent in mice. In contrast, a control virus with the HA and NA from a more recent human isolate was unable to kill mice at any dose tested. The recombinant viruses were also tested for their sensitivity to U.S. Food and Drug Administration-approved antiinfluenza virus drugs in vitro and in vivo. Recombinant viruses possessing the 1918 NA or both the 1918 HA and 1918 NA were inhibited effectively in both tissue culture and mice by the NA inhibitors, zanamivir and oseltamivir. A recombinant virus possessing the 1918 M segment was inhibited effectively both in tissue culture and in vivo by the M2 ion-channel inhibitors amantadine and rimantadine. These data suggest that current antiviral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus.

Authors+Show Affiliations

Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12368467

Citation

Tumpey, Terrence M., et al. "Existing Antivirals Are Effective Against Influenza Viruses With Genes From the 1918 Pandemic Virus." Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 21, 2002, pp. 13849-54.
Tumpey TM, García-Sastre A, Mikulasova A, et al. Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. Proc Natl Acad Sci USA. 2002;99(21):13849-54.
Tumpey, T. M., García-Sastre, A., Mikulasova, A., Taubenberger, J. K., Swayne, D. E., Palese, P., & Basler, C. F. (2002). Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. Proceedings of the National Academy of Sciences of the United States of America, 99(21), pp. 13849-54.
Tumpey TM, et al. Existing Antivirals Are Effective Against Influenza Viruses With Genes From the 1918 Pandemic Virus. Proc Natl Acad Sci USA. 2002 Oct 15;99(21):13849-54. PubMed PMID: 12368467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. AU - Tumpey,Terrence M, AU - García-Sastre,Adolfo, AU - Mikulasova,Andrea, AU - Taubenberger,Jeffery K, AU - Swayne,David E, AU - Palese,Peter, AU - Basler,Christopher F, Y1 - 2002/10/04/ PY - 2002/10/9/pubmed PY - 2002/12/5/medline PY - 2002/10/9/entrez SP - 13849 EP - 54 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 99 IS - 21 N2 - The 1918 influenza pandemic caused more than 20 million deaths worldwide. Thus, the potential impact of a re-emergent 1918 or 1918-like influenza virus, whether through natural means or as a result of bioterrorism, is of significant concern. The genetic determinants of the virulence of the 1918 virus have not been defined yet, nor have specific clinical prophylaxis and/or treatment interventions that would be effective against a re-emergent 1918 or 1918-like virus been identified. Based on the reported nucleotide sequences, we have reconstructed the hemagglutinin (HA), neuraminidase (NA), and matrix (M) genes of the 1918 virus. Under biosafety level 3 (agricultural) conditions, we have generated recombinant influenza viruses bearing the 1918 HA, NA, or M segments. Strikingly, recombinant viruses possessing both the 1918 HA and 1918 NA were virulent in mice. In contrast, a control virus with the HA and NA from a more recent human isolate was unable to kill mice at any dose tested. The recombinant viruses were also tested for their sensitivity to U.S. Food and Drug Administration-approved antiinfluenza virus drugs in vitro and in vivo. Recombinant viruses possessing the 1918 NA or both the 1918 HA and 1918 NA were inhibited effectively in both tissue culture and mice by the NA inhibitors, zanamivir and oseltamivir. A recombinant virus possessing the 1918 M segment was inhibited effectively both in tissue culture and in vivo by the M2 ion-channel inhibitors amantadine and rimantadine. These data suggest that current antiviral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/12368467/Existing_antivirals_are_effective_against_influenza_viruses_with_genes_from_the_1918_pandemic_virus_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=12368467 DB - PRIME DP - Unbound Medicine ER -