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As you know, I have been kvetching recently about the potential for a hybrid (or maybe "hybird," as I originally typed, in error but perhaps a Freudian slip?), avian/human flu virus to emerge from somewhere other than here.

Today, respected researcher Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison (left) has issued a paper where he postulates that such an occurrence is not only possible -- he has done it. 

Let's read the release and then talk.  From the University of Wisconsin-Madison press release:

VIRUS HYBRIDIZATION COULD CREATE PANDEMIC BIRD FLU

MADISON - Genetic interactions between avian H5N1 influenza and human seasonal influenza viruses have the potential to create hybrid strains combining the virulence of bird flu with the pandemic ability of H1N1, according to a new study.

In laboratory experiments in mice, a single gene segment from a human seasonal flu virus, H3N2, was able to convert the avian H5N1 virus into a highly pathogenic form. The findings are reported the week of Feb. 22 in the online early edition of the Proceedings of the National Academy of Sciences.

"Some hybrids between H5N1 virus and seasonal influenza viruses were more pathogenic than the original H5N1 viruses. That is worrisome," says Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison and senior author of the new study.

The H5N1 bird flu virus has spread worldwide through bird populations and has caused 442 confirmed human cases and 262 deaths, according to the World Health Organization. To date, however, bird flu has not been able to spread effectively between people.

"H5N1 virus has never acquired the ability to transmit among humans, which is why we haven't had a pandemic. The worry is that the pandemic H1N1 virus may provide that nature in the background of this highly pathogenic H5N1 virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine.

Two viruses infecting a single host cell can swap genetic material, or reassort, creating hybrid strains with characteristics of each parent virus.

Before the current study, hybrid viruses generated in lab studies had always been less virulent than parent strains. However, the new findings raise concerns that H5N1 and pandemic H1N1 viruses could reassort in individuals exposed to both viruses and generate an influenza strain that is both highly virulent and contagious.

The increased virulence seen in the new study seems to arise from one of the eight genes in the viral genome, called PB2, which is known to affect how well the bird flu virus grows in mammalian hosts, including humans. When tested in mice, the human virus version of PB2 swapped into H5N1 converted the avian virus to a highly pathogenic form.

The researchers say surveillance of viral populations is critical to monitor the potential emergence of highly pathogenic viral variants due to reassortment of avian and human influenza viruses. Their results, including identification of the PB2 segment as a key to enhanced virulence, offer information likely to be useful in the event of a pandemic caused by a hybrid avian-human influenza strain.

"With the new pandemic H1N1 virus, people sort of forgot about H5N1 avian influenza. But the reality is that H5N1 avian virus is still out there," Kawaoka says. "Our data suggests that it is possible there may be reassortment between H5 and pandemic H1N1 that can create a more pathogenic H5N1 virus."

The work was funded by the U.S. National Institutes of Health, the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Japan Science and Technology Agency. (bold mine)

Dr. Kawaoka's research is getting a lot of attention, including a recent grant from the Bill and Melinda Gates Foundation.  What is so interesting about Dr. Kawaoka's recent experiments is that he targeted PB2, the segment which few know enough about to be decisive.  Dr. Kawaoka and his research team have taken a human PB2 gene segment and spliced it to H5N1 bird flu.  The result is a more lethal and even more virulent virus than the parent H5N1 strain!

Dr. Kawaoka and his staff have now, and pretty conclusively, named PB2 as the gene segment responsible for lethality in humans.  In prepping for this blog, I stumbled across a blogsite by the name of Monotreme's Blog, and how I never saw it before now is a mystery to me.  Anyway, this blog has an interesting confirmation of Kawaoka's discovery.  But it turns things in a different direction than an avian/swine hybrid doomsday virus.  From Monotreme's Blog entry of December 2, 2009:

The PB2 gene is reported to be key in the adaptation of a virus that infects birds to one that infects humans. In particular, it has been reported that the amino acid at position 627 is critical for this adaptation (Van Hoeven et al. 2009). Viruses that infect birds typically have a glutamic acid (E) in this position. Flu A viruses that are fully adapted to humans usually have a lysine (K) at this position. This same position in PB2 appears to be key in determining the lethality of flu viruses (Hatta et al. 2001). In the 1918 pandemic and H5N1 viruses, a lysine in this position is associated with a higher level of lethality. The presence of a lysine at position 627 appears to permit flu viruses to replicate in both the lungs and nose and thus spread more easily from person to person.

It is possible, perhaps likely, that as pandemic H1N1 adapts to humans, a mutation will occur that will create a lysine in position 627 in this virus. If so, will the virus become more virulent? At this point, it is difficult to say. On the one hand, “seasonal” flu viruses that are not considered particularly lethal have a lysine at position 627. On the other hand, a change from glutamic acid, when the virus is infecting birds, to a lysine, when the virus is starts to infect humans, is associated with much greater virulence. How to reconcile these apparently contradictory facts? It may be that the change to a lysine is initially associated much greater virulence due to interactions with other proteins. As the virus moves through the human population immune responses are triggered. Thus, a year or two after a pandemic begins, the virus comes under selection to escape immune system detection. This selection may result in the preferential propagation of new versions of other proteins which no longer interact with PB2 to create a more lethal virus. In this scenario, a mutation at position 627 from gluatamic acid to lysine will initially create a more lethal virus, but, as the virus is “tamed” by the immune system selection, this mutation will utlimately be insufficient to sustain a high degree of lethality.

Given that human-adapted flu A viruses tend to have a lysine at position 627, it seems likely that the new pandemic H1N1 will eventually lose its “avian” glutamic acid and acquire a lysine at this position. There have already been sporadic instances of this. If/when this occurs in a strain that spreads widely, it would not be surprising if it becomes more lethal.

Kawaoka's research has taken Monotreme's (and others') speculation and turned it into fact.  

Monotreme offers a theory that immune responses in humans will ultimately steer this lysine-altered virus toward a less lethal path in order for it to evade antibody detection and eradication.  But how long will that process take, and how many lives would be impacted by the virus in the meantime, are only known to God.

In the meantime, bird flu continues to buck the tradition of flu viruses during a pandemic.  this virus refuses to go away.  Just today, comes word of two more Egyptians struck down with H5N1 bird flu.

Now I am going to make a statement, and I want you to read it and absorb it.

There have been more Egyptians hit by H5N1 bird flu thus far in 2010 than there are Americans who have tested positive for H1N1 or H3N2 seasonal influenza.

Bird flu continues to spread again, in defiance of tradition and in defiance of all governments' attempts to eradicate it.  As the H1N1v pandemic continues to strike and spread in Asia, the potential for dual infection with H5 and H1 simultaneously increases.  How many cross-infections does it take to achieve some sort of viral critical mass?

Only one.