H9N2 Avian flu and H1N1 pandemic: High genetic compatibility and increased pathogenicity of reassortants

H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health.

The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort.

To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice.

These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses.

All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk.

Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity.

Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.

Read the full paper at PNAS website:
High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses

H5N1: Influenza detector gene stops virus transmission to humans

Katharine Magor, a U of A associate professor of biology, has identified the genetic detector that allows ducks to live, unharmed, as the host of influenza.

The duck's virus detector gene, called retinoic acid inducible gene -- I, or RIG-I, enables a duck's immune system to contain the virus, which typically spreads from ducks to chickens, where it mutates and can evolve to be a human threat like the H5N1 influenza virus.

The first human H5N1 cases were in Hong Kong in 1997. Eighteen people with close contact to chickens became infected and six died.

Magor's research shows chickens do not have a RIG-I gene. A healthy chicken can die within 18 hours after infection, but researchers have successfully transferred the RIG-I gene from ducks to chicken cells. The chicken's defenses against influenza were augmented and RIG-I reduced viral replication by half.

One potential application of this research could affect the worldwide poultry industry by production of an influenza-resistant chicken created by transgenesis.

The work of Katharine Magor, her U of A PhD candidate Megan Barber, and researchers from the United States (Jerry Aldridge and Robert Webster) was published March 22, in the online, early edition of Proceedings from the National Academy of Sciences.

For further information check out the Univeristy of Alberta website

H5N1 Avian Flu: New Outbreak in Romania

A suspected bird flu outbreak has been reported in a remote Romanian village, the Sanitary and Veterinary Authority said Saturday.

Samples of two dead hens were sent for confirmation of the potentially deadly H5N1 virus to the Animal Health Institute in Bucharest and on to the Weybridge laboratory in Britain, the Authority said.

The poultry in the small private farm at a village on the Danube Delta were slaughtered and the area disinfected.

"There is currently no risk of the disease spreading," the Authority said.

Two weeks ago, a bird flu outbreak was reported in the nearby village of Letea close to the Ukrainian border, the first case in Europe for a year.

The previous case in the European Union had been confirmed in March 2009 in a wild duck shot during a hunt near Starnberg, in Bavaria, southern Germany.

Romania was hit by massive bird flu outbreaks in 2005 and 2006, when more than a million poultry were slaughtered.

Avian influenza or "bird flu" is a highly contagious viral disease which primarily affects birds, but on rare occasions can also be contracted by humans and other mammals.

On Wednesday, the World Health Organisation said the H5N1 virus remains a threat to humans, after bird flu outbreaks killed seven people in several countries since the beginning of the year.

H5N1 Avian flu Bangladesh: 117,000 birds slaughtered to stem infection

At least 117,000 chickens were destroyed in northern Bangladesh Sunday after avian flu outbreak on one of the country's largest poultry farms, a local official said.

The deadly H5N1 strain of flu was detected on Saturday when 400 chickens died suddenly at the Kazi Farms complex in Thakurgaon town, district livestock chief Mosaddekur Rahman reported.

"Tests confirmed presence of the H5N1 bird flu in 15 sheds of the farm and we ordered destruction of all 117,600 layer chickens," he said.

Kazi Farms is Bangladesh's largest poultry bird and egg producer. General manager of the company Ataur Rahman said another 200,000 eggs had also been destroyed in the single largest outbreak of bird flu in the country.

"Our loss will be more than 400 million taka (six million dollars)," he said.

Bangladesh was hit by bird flu in February 2007, when more than one million birds were slaughtered on thousands of farms across the country.

The last major outbreak was in November 2008 when 10,000 birds were culled over a two-month period, with smaller outbreaks detected in 2009.

Bangladesh's poultry industry is one of the world's largest, producing 220 million chickens and 37 million ducks annually.

The country reported its first confirmed human case of bird flu in May 2008, but the government said the 16-month-old baby who contracted the virus recovered.

H5N1 Avian Flu: Labs Producing Virulent Flu Strains

Engineered hybrids of H5N1 bird flu and H1N1 human flu strains have proven virulent in mice, raising the danger that a natural recombination would be deadly to humans.

For years, researchers have worried that H5N1 avian influenza would mix with human flu viruses, evolving into a form that keeps its current lethality but is far more contagious.

That hasn’t happened in the wild yet but the latest findings, published Feb. 22 in the Proceedings of the National Academy of Sciences, show how easily it can happen.

Mind the Gap
“Fortunately, the H5N1 viruses still lack the ability to transmit efficiently among humans.” However, the virus may soon be overcome this obstacle when it mixes with human flu strains. These are the findings of researchers led by University of Wisconsin virologist Yoshihiro Kawaoka. “The next pandemic is inevitable and it will be more devastating than the last.”

Current strains of H5N1 have infected 478 people since 2003, and killed 286 of them. It’s has difficulty transmitting to humans. It requires close contact and exposure to an infected person, bird or animal.

H5N1 in Birds
In birds, however, H5N1 is far more contagious, and here the virus has killed tens of millions of fowl. Fortunately, cases have been concentrated in Africa and Eurasia, but as the swine flu pandemic demonstrated, any flu contagious to humans will quickly spread on a global scale. This is mainly thanks to air travel and the free movement of peoples across state boundaries.

Influenza viruses mutate and swap genes easily, with co-infections turning animals into mobile petri dishes. In 2008, hoping to learn more about how H5N1 might evolve, researchers from the Centers for Disease Control and Prevention combined it with a common human flu strain.

The researchers engineered all 254 possible variants of hybridisation between the deadly H5N1 avian flu strain found in Borneo, and a, H1N1 human flu virus from Tokyo. They identified three strains that were both contagious and deadly, in mice.

The New Pandemic
A flu virus that kills mice won’t necessarily kill humans, but the results are very disturbing. All three killer hybrid strains possessed a protein taken from the human strain. Called PB2, the protein appeared to help the virus survive in the mice’s upper respiratory tract. As of now, bird flu stays in the lower respiratory tract, where it’s less likely to be casually transmitted.

Although the recent H1N1 pandemic has not proved to be as lethal as originally feared, it certainly exposed how unprepared the world is for new influenza strains. At the same time it also exposed the ability of pharmaceutical companies to frighten the WHO, governments and politicians into spending $Millions to stockpile ineffective vaccines.

Source of Infection
In May, Hong Kong University virologist Yi Guan, best known for finding the animal origin of SARS, was asked by Science Insider about the possibility of H5N1 and swine flu mixing.

“If that happens, I will retire immediately and lock myself in a sealed laboratory", said Guan. "But, historically the Chinese mainland would be the most likely source of such a virus."

Global Alert
Unfortunately, in such a situation, the imposed cover-up by local authorities would mean that the virus will have spread with a high rate of cross-infection and will have escaped globally, even before we are alerted to it's existance. We will not be alerted until it has spread to the Western world and many people have become infected and died.

Lethal Viruses Escape
The other issue is the development of virulent and lethal strains in laboratories and institutions. There has been a sad history of viruses erroneously 'escaping' from pharmaceutical labs and there is no reason to believe that this will not happen in the future, despite due diligence.

Mitigation
Should we live our lives in a bubble? No, definitely not but we should be aware of the dangers we are facing and how these may manifest themselves. Yes, there is a lethal danger from a mutant virus but this danger is greater if the world's health authorities are not communicating properly or collaborating on a global scale and this is something that can be mitigated against.