Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses

@article{Hatta2001MolecularBF,
  title={Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses},
  author={Masato Hatta and Peng Gao and Peter J. Halfmann and Yoshihiro Kawaoka},
  journal={Science},
  year={2001},
  volume={293},
  pages={1840 - 1842}
}
  • M. Hatta, Peng Gao, +1 author Y. Kawaoka
  • Published 7 September 2001
  • Biology, Medicine
  • Science
In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection. 
Factors determining the high pathogenicity of Hong Kong H5N1/97 influenza viruses in mammals
TLDR
The possibility that in some instances the unusual severity of H5N1 virus-induced disease in mice is due to a cytokine imbalance caused by the virus's NS gene is discussed. Expand
Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013.
  • T. Kageyama, S. Fujisaki, +7 authors M. Tashiro
  • Biology, Medicine
  • Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
  • 2013
TLDR
Several characteristic amino acid changes in HA and the PB2 RNA polymerase subunit probably facilitate binding to human-type receptors and efficient replication in mammals, respectively, highlighting the pandemic potential of the novel viruses. Expand
Molecular Pathogenesis of H5N1 Influenza Virus Infections
TLDR
The molecular features of H5N1 influenza viruses that might affect their pathogenicity are discussed, and the current lack of efficient human-to-human transmission is explained. Expand
Mammalian Adaptation in the PB2 Gene of Avian H5N1 Influenza Virus
TLDR
The E-to-K host-adaptive mutation in the PB2 gene appeared from day 4 and 5 along the respiratory tracts of mice and was complete by day 6 postinoculation, correlated with efficient replication of the virus in mice. Expand
Human Infection from Avian-like Influenza A (H1N1) Viruses in Pigs, China
TLDR
It was found that the influenza virus showed high sequence identity to that of swine, and serologic evidence indicated that viral persistence in pigs was the source of infection. Expand
Characterization of low-pathogenic H6N6 avian influenza viruses in central China
Three strains of H6N6 subtype avian influenza virus (AIV) were isolated from live-poultry markets of central China during 2009-2010. A phylogenetic analysis showed that these isolates originated fromExpand
Selection of H5N1 Influenza Virus PB2 during Replication in Humans
TLDR
A direct analysis of the viral RNAs of H5N1 viruses in patients revealed that these amino acids contribute to efficient virus propagation in the human upper respiratory tract. Expand
Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam
TLDR
The sequences of all eight genes of 22 human isolates collected between 2003 and 2008 and compared their virulence in mice indicated that asparagine at position 701 of PB2 and other unknown virulence determinants appear to be involved in the high pathogenicity of clade 1 viruses, warranting further studies to determine the factors responsible for the high virulence of H5N1 viruses in mammals. Expand
Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice.
TLDR
Multiple genes are involved in virulence of Hong Kong H5N1 influenza A viruses for mice with the presence of lysine at aa627 in the PB2 gene exhibiting a significantly larger effect than the HA and NA genes. Expand
Genetic properties and pathogenicity of a novel reassortant H10N5 influenza virus from wild birds
TLDR
The genome of a H10N5 influenza virus from wild birds was analyzed and mouse-adapted viruses bearing mutations PB2-E627K and HA-G218E were generated, suggesting that the pathogenicity of low pathogenic H 10N5 in chickens can be enhanced after passage in mammals. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 19 REFERENCES
Molecular Correlates of Influenza A H5N1 Virus Pathogenesis in Mice
TLDR
Sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice and are the likely determinants of virulence of human H5N1 influenza viruses in this model. Expand
Biological Heterogeneity, Including Systemic Replication in Mice, of H5N1 Influenza A Virus Isolates from Humans in Hong Kong
  • Peng Gao, Shinji Watanabe, +5 authors Y. Kawaoka
  • Biology, Medicine
  • Journal of Virology
  • 1999
TLDR
The ability of these H5N1 viruses to produce systemic infection in mice and the clear differences in pathogenicity among the isolates studied here indicate that this system provides a useful model for studying the pathogenesis of avian influenza virus infection in mammals. Expand
Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.
TLDR
An avian H5N1 influenza A virus was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza, causing 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. Expand
Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus
TLDR
The results suggest transmission of the virus from infected chickens to the child without another intermediate mammalian host acting as a "mixing vessel" illustrates the importance of intensive global influenza surveillance. Expand
A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans
TLDR
This is the first demonstration of an influenza A virus that replicates systemically in a mammalian species and is neurotropic without prior adaptation and suggests a strategy of vaccine preparedness for rapid intervention in future influenza pandemics that uses antigenically related nonpathogenic viruses as vaccine candidates. Expand
Direct sequencing of the HA gene of influenza (H3N2) virus in original clinical samples reveals sequence identity with mammalian cell-grown virus
TLDR
C cultivation of human influenza H3N2 virus in mammalian MDCK cells results in a virus similar to the predominant population of virus found in the infected individual, which is distinct from the HA of viruses grown in eggs. Expand
Comparisons of Highly Virulent H5N1 Influenza A Viruses Isolated from Humans and Chickens from Hong Kong
TLDR
A small number of changes in hemagglutinin gene sequences defined two closely related subgroups, with both subgroups having human and chicken members, among the seven viruses examined from Hong Kong, and all seven viruses were highly pathogenic in chickens and caused similar lesions in experimental inoculations. Expand
Attenuation of pathogenicity of fowl plague virus by recombination with other influenza A viruses nonpathogenic for fowl: nonexculsive dependence of pathogenicity on hemagglutinin and neuraminidase of the virus
TLDR
It is concluded that the surface components do not by themselves determine the pathogenicity of influenza A viruses. Expand
A single amino acid in the PB2 gene of influenza A virus is a determinant of host range
TLDR
The nucleotide sequences of thePB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu-->Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells. Expand
Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells.
  • Y. Kawaoka, R. Webster
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1988
TLDR
The HA gene from a virulent H5 influenza virus was expressed in mammalian cells, and the cleavage site of the HA was explored by using site-specific mutagenesis to establish that most of the basic amino acids at this site are critical for cleavage activation. Expand
...
1
2
...