Very Interesting!! H1N1 lacks PB2!! shouldn't be able to jump species!!

This research is scary on a number of levels.

CTV TORONTO

Transmission studies suggest H1N1 is here to stay

Updated: Thu Jul. 02 2009 2:13:51 PM

The Canadian Press

TORONTO — H1N1 viruses are missing at least two key features seen in all flu viruses present and past that transmit well among people and yet the viruses are spreading quite efficiently, two new studies suggest.

The research groups which produced the work differ slightly in their views of the degree to which the novel H1N1 virus is spreading, with one finding transmission isn't yet as efficient as with human flu viruses while the other finding transmission rates are in lockstep with those of seasonal flu cousins.

There is no disputing the evidence, though -- the virus is spreading around the globe, claiming at least 332 lives so far. And it is doing this without all the tools scientists would expect a flu virus to need to become a successful human pathogen.

"The take-home message is that a virus that does not have some of the features that we have previously recognized as hallmarks of adaptation of flu in humans was able to establish itself in humans and cause disease," said Dr. Daniel Perez, an influenza virologist with the University of Maryland.

"Regardless of what the virus might do, I believe it is here to stay either as a whole virus or with some of its gene. It may be able to outcompete and-or co-circulate with seasonal flu strains."

Perez was not involved in the studies, both of which will be published Friday in the journal Science. He is, however, familiar with the work; his lab has completed a similar study.

The transmission studies were done by research groups at the U.S. Centers for Disease Control with colleagues from the Massachusetts Institute of Technology and at Erasmus Medical Center in Rotterdam, the Netherlands.

Both groups tested spread in ferrets, which are considered an excellent model for flu infection in humans.

The CDC's work suggests the virus isn't yet completely adapted to spread among humans. When healthy ferrets were housed in cages adjacent to and sharing feeding dishes with experimentally infected animals, only two-thirds of the healthy animals became infected in the CDC research.

By contrast, the group in the Netherlands found all healthy ferrets caught the new virus when housed next to animals infected with the virus. Perez's work also saw this 100 per cent transmission rate.

In both the CDC and Erasmus studies, ferrets that were infected with human flu viruses transmitted infection to all their healthy neighbours.

Dr. Terrence Tumpey, senior author of the CDC study, said variation in the air flow setups between the CDC's ferret cages and those used in the other studies may explain the differing findings.

But based on what they saw, his team believes this virus may still be getting used to its new human host.

A key piece of evidence supporting their conclusion relates to the virus's ability to infect cells in the human respiratory tract. The CDC-MIT scientists showed the novel H1N1 virus's hemagglutinin -- the surface protein that locks onto a cell it is about to invade -- currently makes a connection that is weaker or less efficient than that made by regular flu viruses.

That suggests the virus has room for improvement. And if it mutates to bind more efficiently, it would become even more adept at spreading from person to person.

"I mean, it's transmitting. But we think it could potentially transmit even better," Tumpey said from Atlanta.

He suggested with better transmission could come more severe disease -- not just in sheer numbers, but in the proportion of infected people who develop serious illness.

"A lot of cases have been mild. But if it was adapted more towards humans, it could be more severe. More consistently severe," Tumpey said.

His counterpart on the Dutch paper, Dr. Ron Fouchier, shares his concerns.

"I do agree that the virus might still pick up mutations to improve infection and transmission in humans. But in our opinion, it is already good enough to beat the seasonal flu viruses," he said via email.

The CDC scientists also reported that the virus is missing a feature in an internal gene called PB2 that is known to relate to transmissibility.

All seasonal flu viruses and the past three pandemic viruses -- in other words, all flu viruses which have successfully made the jump from other species into humans -- have had this feature. The H1N1 virus does not.

They don't know how the virus achieved transmissibility without this mutation or how likely it is to acquire it. But Tumpey said the mutation is also linked to increased virulence or disease severity and the flu community is watching closely for this change.

Both groups studied tissues from the infected ferrets. They found H1N1 viruses triggered infections that went deep into the lungs of the animals. Human flu strains infect the animals' upper airways.

That ability of the virus to spread to and proliferate deep in the lungs could help explain what doctors caring for severely ill H1N1 patients are seeing: aggressive viral pneumonias that incapacitate the lungs.

"Certainly, the lesions we noted in our ferrets are consistent with the disease in humans," Fouchier said.

"It seems that due to more extensive virus replication, the virus does more damage, and spreads deeper down the airways as compared to seasonal viruses."

Those findings are concerning, suggested Dr. Malik Peiris, a virologist and flu expert at the University of Hong Kong.

Peiris, who was not involved in the studies, said that while the H1N1 virus is not as virulent as H5N1 avian influenza or the virus that caused the 1918 Spanish flu, its ability to infect the lower respiratory tract "is clearly cause for caution in regard to the pathogenic potential of this virus in humans."

Both H5N1 and the Spanish flu virus infect tissues deep in the lungs.

Fouchier said he is concerned the novel H1N1's ability to invade deep lung tissue could lead to more severe disease when the virus is spreading in true winter conditions, which are better suited to spread of flu.

A study in guinea pigs -- also a good animal model for flu -- published a couple of years ago found that at lower temperatures flu viruses replicate more and for longer durations.

If that holds true for humans and for this virus, the severity of H1N1 infections in winter could be greater, Fouchier warned.