RECENT ADVANCES IN H5N1 INFLUENZA VIRUS RESEARCH
Although the newspapers no longer carry headlines of the fears of a world-wide bird flu pandemic, the threat still remains. Public health officials make it very clear this virus can readily mutate into a virus ever bit as threatening in humans as it has become in birds. For example, India is in the midst of a significant outbreak in poultry and there is much concern by the health experts to keep the disease from spreading into Calcutta, a city of 14 million people. Of significance, a total of 14 countries have reported human infections, with Pakistan and Myanmar being the most recent in reporting their first infections. Moreover, it will be of extreme interest to observe the overall public health effects of the million or so homeless people devastated in Myanmar as a result of the recent cyclone.
To date, approximately 220 humans have died from the avian flu virus. All those who died had close contact with the virus from infected birds and/or fowl. However, the real concern is that the flu virus mutates quickly and the H5N1 virus is no exception. The threat is far from over.
Since the next influenza pandemic will very likely be caused by the H5N1 influenza virus, two recent articles in the March 2008 issue of the "Journal of Virology " indicate strong vaccine possibilities. The paper by Jiao et al reported on the single change substitution of an amino acid that appears to alter the virulence of the H5N1 virus. They demonstrated that serine 42 in the viral NS1 protein plays a critical role in the pathogenicity of H5N1 virus in mammalian hosts. These investigators believe their results provided strong evidence that the NS1 protein is a virulence factor for H5N1 influenza viruses and that multiple domains within NS1 may be targets for the development of a antiviral drugs and attenuated vaccines (J. Virol., 2008, 82:1146-1154).
In the second article, Watanabe and co-workers have been looking at the M2 protein that consists of three structural domains, one of which is a 54-amino acid cytoplasmic tail domain in the influenza A virus. In a previous study they demonstrated that deleting the M2 cytoplasmic tail caused a growth defect in the H1N1 influenza virus suggesting that the M2 cytoplasmic tail plays a vital role in virus replication. In their current study these investigators created an M2 tail mutant H5N1 virus, vaccinated mice with it, and challenged the mice with a lethal dose of H5N1 influenza virus. Their results showed that the mice were protected from death suggesting that the virus could not replicate and therefore be used as a vaccine ( J. Virol., 2008, 82: 2486 – 2492 ).