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Science 24 December 1982:
Vol. 218. no. 4579, pp. 1330 - 1332
DOI: 10.1126/science.6183749
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Articles

Science, Vol 218, Issue 4579, 1330-1332
Copyright © 1982 by American Association for the Advancement of Science

articles

Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys

BR Murphy, DL Sly, EL Tierney, NT Hosier, JG Massicot, WT London, RM Chanock, RG Webster, and VS Hinshaw

An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication is squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistant to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs.
R. Manzoor, Y. Sakoda, N. Nomura, Y. Tsuda, H. Ozaki, M. Okamatsu, and H. Kida (2009)
J. Virol. 83, 1572-1578
   Abstract »    Full Text »    PDF »
The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunit.
B. G. Bradel-Tretheway, Z. Kelley, S. Chakraborty-Sett, T. Takimoto, B. Kim, and S. Dewhurst (2008)
J. Gen. Virol. 89, 2923-2932
   Abstract »    Full Text »    PDF »
An avian live attenuated master backbone for potential use in epidemic and pandemic influenza vaccines.
D. Hickman, M. J. Hossain, H. Song, Y. Araya, A. Solorzano, and D. R. Perez (2008)
J. Gen. Virol. 89, 2682-2690
   Abstract »    Full Text »    PDF »
Characterization of Avian H3N3 and H1N1 Influenza A Viruses Isolated from Pigs in Canada.
A. I. Karasin, K. West, S. Carman, and C. W. Olsen (2004)
J. Clin. Microbiol. 42, 4349-4354
   Abstract »    Full Text »    PDF »
Determinants of the Host Range Restriction of Replication of Bovine Parainfluenza Virus Type 3 in Rhesus Monkeys Are Polygenic.
M. H. Skiadopoulos, A. C. Schmidt, J. M. Riggs, S. R. Surman, W. R. Elkins, M. St. Claire, P. L. Collins, and B. R. Murphy (2002)
J. Virol. 77, 1141-1148
   Abstract »    Full Text »    PDF »
Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses.
M. Hatta, P. Gao, P. Halfmann, and Y. Kawaoka (2001)
Science 293, 1840-1842
   Abstract »    Full Text »    PDF »
Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential.
T. Ito, J. N. S. S. Couceiro, S. Kelm, L. G. Baum, S. Krauss, M. R. Castrucci, I. Donatelli, H. Kida, J. C. Paulson, R. G. Webster, et al. (1998)
J. Virol. 72, 7367-7373
   Abstract »    Full Text »    PDF »


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