Manipulating a previously identified protein may be the key to developing an effective H5N1 influenza A virus vaccine say researchers from the University of Wisconsin-Madison and the University of Tokyo.
Since its emergence in 1997, the highly pathogenic avian influenza virus (H5N1) has affected wild birds and poultry in more than 10 Asian countries as well as Europe and Africa. A total of 321 confirmed human cases have occurred since late 2003 resulting in 194 deaths and a fatality rate of approximately 60%. Although there are currently some antiviral drugs available for treatment of influenza virus infection, H5N1 has proven resistant to most, therefore emphasizing the need for an effective vaccine.
The influenza A virus M2 protein consists of three structural domains, one of which is a 54-amino acid cytoplasmic tail domain. In a previous study the researchers demonstrated that deleting the M2 cytoplasmic tail caused a growth defect in the H1N1 influenza virus, indicating that the M2 cytoplasmic tail plays a vital role in virus replication. In the current study they created an M2 tail mutant H5N1 virus, vaccinated mice with it and challenged the mice with a lethal dose of influenza virus. Results showed that the mice were protected from death suggesting that the virus could not replicate and could therefore be used as a vaccine.
"Here, we demonstrate that an M2 cytoplasmic tail deletion mutant protects mice from lethal challenge with a highly pathogenic H5N1 virus, suggesting the potential of M2 tail mutants as live attenuated vaccines against H5N1 influenza virus infection," say the researchers.
Journal reference: T. Watanabe, S. Watanabe, J. Hyun Kim, M. Hatta, Y. Kawaoka. 2008. Novel approach to the development of effective H5N1 influenza A virus vaccines: use of M2 cytoplasmic tail mutants. Journal of Virology, 82. 5: 2486-2492.
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