June 13, 2009

New Insights Into Novel H1N1

Electron micrograph image of an influenza virus Electron micrograph of an influenza virus. Dr. Erskine L. Palmer and Dr. M. L. Martin, CDC.

This spring, a new influenza, or flu, virus began causing illness in people around the world. Originally called "swine flu" because it's a descendant of viruses that have long infected pigs, the virus is now called "novel H1N1." Several new studies have revealed where the virus came from and given insight into how dangerous it might become.

Influenza viruses have 8 genes, 2 of which—hemagglutinin (H) and neuraminidase (N)—code for proteins on the virus surface that allow the virus to enter and spread from cell to cell. There are 16 H subtypes and 9 N subtypes, making 144 possible HN combinations. Subtle variations in these 2 proteins affect how easily the viruses infect people and whether the immune system can recognize them.

Several research groups funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of General Medical Sciences (NIGMS) have recently put together a picture of where the novel H1N1 virus came from and how it evolved. They discovered that the novel H1N1 virus is a descendent not only of swine viruses but also of the H1N1 virus that caused the 1918 pandemic, which killed 40-50 million people worldwide.

"The 1918-1919 influenza pandemic was a defining event in the history of public health," says NIAID Director Dr. Anthony S. Fauci. "The legacy of that pandemic lives on in many ways, including the fact that the descendents of the 1918 virus have continued to circulate for 9 decades."

In other work, 2 research groups—an NIGMS-funded team at the Massachusetts Institute of Technology and researchers at the Centers for Disease Control and Prevention (CDC)—recently collaborated to test the ability of novel H1N1 to spread and cause disease. They isolated viruses from 3 patients and infected mice and ferrets. The results were published online ahead of print on July 2, 2009, in Science.

The researchers found that, compared to seasonal H1N1 flu viruses, the novel H1N1 viruses replicated to higher levels in lung tissue and were also more deadly. The scientists also found the viruses in the intestinal tracts of the ferrets, which might explain reports of gastro-intestinal problems in some infected people. However, the novel H1N1 viruses transmitted less efficiently between ferrets in respiratory droplets than seasonal H1N1.

The binding of influenza viruses to their target cells is mediated by hemagglutinin. The researchers found that the novel H1N1 hemagglutinin binds to receptors in the human respiratory tract much less effectively than other flu viruses that infect humans. However, flu viruses can mutate rapidly, so the virus could potentially improve its ability to bind.

The researchers also found that novel H1N1 doesn't have a version of another gene called PB2 that has been associated with efficient virus transmission. However, they point out that the virus could acquire another version of the gene through mutation or by exchanging genes with other influenza viruses.

These recent insights into how novel H1N1 arose and how it spreads will be crucial for stopping a pandemic. "We need to pay careful attention to the evolution of this virus," says Dr. Ram Sasisekharan, who led the MIT research team.

—by Harrison Wein, Ph.D.

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