Recent Advances in H5N1 Influenza Virus Research

Bill Martin


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 ).

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1 Comment

  1. Spread of avian flu by drinking water:
    Spread of avian flu by drinking water can explain small clusters in households.
    Proved awareness to ecology and transmission is necessary to understand the spread of avian flu. For this it is insufficient exclusive to test samples from wild birds, poultry and humans for avian flu viruses. Samples from the known abiotic vehicles also have to be analysed. There are plain links between the cold, rainy seasons as well as floods and the spread of avian flu. That is just why abiotic vehicles have to be analysed. The direct biotic transmission from birds, poultry or humans to humans can not depend on the cold, rainy seasons or floods. Water is a very efficient abiotic vehicle for the spread of viruses – in particular of fecal as well as by mouth, nose and eyes excreted viruses.
    Infected birds and poultry can everywhere contaminate the drinking water. All humans have very intensive contact to drinking water. To prove viruses in water is difficult because of dilution. If you find no viruses you can not be sure that there are not any. On the other hand in water viruses remain viable for a long time. Water has to be tested for influenza viruses by cell culture and in particular by the more sensitive molecular biology method PCR.
    There is a widespread link between avian flu and water, e.g. in Egypt to the Nile delta or Indonesia to residential districts of less prosperous humans with backyard flocks and without central water supply as in Vietnam: See also the WHO web side: .
    Transmission of avian flu by direct contact to infected poultry is an unproved assumption from the WHO. There is no evidence that influenza primarily is transmitted by saliva droplets: “Transmission of influenza A in human beings” .
    Avian flu infections may increase in consequence to increase of virus circulation. In hot climates/the tropics flood-related influenza is typical after extreme weather and floods. Virulence of influenza viruses depends on temperature and time. Special in cases of local water supplies with “young” and fresh H5N1 contaminated water from low local wells, cisterns, tanks, rain barrels, ponds, rivers or rice paddies this pathway can explain small clusters in households. At 24°C e.g. in the tropics the virulence of influenza viruses in water amount to 2 days. In temperate climates for “older” water from central water supplies cold water is decisive to virulence of viruses. At 7°C the virulence of influenza viruses in water amount to 14 days.
    Human to human and contact transmission of influenza occur – but are overvalued immense. In the course of influenza epidemics in Germany, recognized clusters are rare, accounting for just 9 percent of cases e.g. in the 2005 season. In temperate climates the lethal H5N1 virus will be transferred to humans via cold drinking water, as with the birds in February and March 2006, strong seasonal at the time when drinking water has its temperature minimum.
    The performance to eliminate viruses from the drinking water processing plants regularly does not meet the requirements of the WHO and the USA/USEPA. Conventional disinfection procedures are poor, because microorganisms in the water are not in suspension, but embedded in particles. Even ground water used for drinking water is not free from viruses.
    Ducks and rice [paddies = flooded by water] major factors in bird flu outbreaks, says UN agency
    Ducks and rice fields may be a critical factor in spreading H5N1
    26 March 2008 – Ducks, rice [fields, paddies = flooded by water! Farmers on work drink the water from rice paddies!] and people – and not chickens – have emerged as the most significant factors in the spread of avian influenza in Thailand and Viet Nam, according to a study carried out by a group of experts from the United Nations Food and Agriculture Organization (FAO) and associated research centres.
    “Mapping H5N1 highly pathogenic avian influenza risk in Southeast Asia: ducks, rice and people” also finds that these factors are probably behind persistent outbreaks in other countries such as Cambodia and Laos.
    The study, which examined a series of waves of H5N1 highly pathogenic avian influenza in Thailand and Viet Nam between early 2004 and late 2005, was initiated and coordinated by FAO senior veterinary officer Jan Slingenbergh and just published in the latest issue of the Proceedings of the National Academy of Sciences of the United States.
    Through the use of satellite mapping, researchers looked at a number of different factors, including the numbers of ducks, geese and chickens, human population size, rice cultivation and geography, and found a strong link between duck grazing patterns and rice cropping intensity.
    In Thailand, for example, the proportion of young ducks in flocks was found to peak in September-October; these rapidly growing young ducks can therefore benefit from the peak of the rice harvest in November-December [at the beginning of the cold: Thailand, Viet Nam, Cambodia, Laos are situated – different from Indonesia – in the northern hemisphere].
    “These peaks in congregation of ducks indicate periods in which there is an increase in the chances for virus release and exposure, and rice paddies often become a temporary habitat for wild bird species,” the agency said in a news release.
    “We now know much better where and when to expect H5N1 flare-ups, and this helps to target prevention and control,” said Mr. Slingenbergh. “In addition, with virus persistence becoming increasingly confined to areas with intensive rice-duck agriculture in eastern and south-eastern Asia, evolution of the H5N1 virus may become easier to predict.”
    He said the findings can help better target control efforts and replace indiscriminate mass vaccination.
    FAO estimates that approximately 90 per cent of the world’s more than 1 billion domestic ducks are in Asia, with about 75 per cent of that in China and Viet Nam. Thailand has about 11 million ducks.
    Dipl.-Ing. Wilfried Soddemann – Epidemiologist – Free Science Journalist

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