Contagious Hybrid Bird Flu-Human Flu Created in Lab
MADISON, Wisconsin, February 26, 2010 (ENS) - Genetic interactions between avian influenza and human seasonal influenza viruses have the potential to create hybrid strains that combine the virulence of bird flu with the ability to spread like a pandemic, new research has found.

"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," says Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison and senior author of the new study.

A new hybrid viral strain could be more capable of producing disease, or pathogenic, than either the bird flu virus or the human flu virus alone.

"Our data suggests that it is possible there may be reassortment between H5 and pandemic H1N1 that can create a more pathogenic H5N1 virus," Kawaoka said.

Professor Yoshihiro Kawaoka (Photo courtesy U. Wisconsin, Madison)

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 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.

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 in the current online early edition of the journal "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," said Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine.

Since the most recent outbreak started in 2003, the H5N1 bird flu virus has spread worldwide through bird populations and has caused 478 confirmed human cases and 286 deaths in 15 countries, according to the latest data from the World Health Organization.

To date, however, bird flu has not been able to spread effectively among 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.

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.

At the same time, Kawaoka and a different set of colleagues have found a novel compound the they say is highly effective against the pathogenic H5N1 avian influenza virus, including some drug-resistant strains.

The research, published today in the Public Library of Science journal PLoS Pathogens, suggests that the compound CS-8958 is a promising alternative antiviral for prevention and treatment of bird flu.

Emerging strains resistant to existing drugs, particularly oseltamivir, sold under the brand name Tamiflu, pose a threat and make the development of alternate antivirals a pressing public health issue, says Kawaoka.

Kawaoka and a group of researchers from Japan, Vietnam, and Indonesia tested a novel neuraminidase inhibitor R-125489 and its prodrug CS-8958, which had previously shown potent activity against seasonal influenza viruses in laboratory animals.

Working with mice, the researchers found that a single intranasal dose of CS-8958 given two hours after infection with H5N1 influenza virus resulted in a higher survival rate and lower virus levels than a standard five-day course of Tamiflu.

"This compound requires only a single administration for both treatment and prophylaxis. Such prophylaxis would be highly desirable for seasonal influenza as well as a potential pandemic situation," says Kawaoka.

Follow-up studies will be needed to confirm the applicability of the findings to humans.

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