Scientists Investigate Severity And Spread Of New H1N1 Swine Flu Virus

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Main Category: Swine Flu
Also Included In: Flu / Cold / SARS;  Infectious Diseases / Bacteria / Viruses
Article Date: 03 Jul 2009 - 2:00 PDT

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Scientists in the US and the Netherlands discovered what most doctors already suspected: the new H1N1 swine flu virus causes more severe infection than seasonal flu, but the two groups disagreed on how easily it spreads, with one finding that it spreads easily while the other finding it does not.

The two studies are published in the 2 July online issue of Science.

In the first study, scientists from the Massachusetts Institute of Technology (MIT) in Cambridge and from the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, assessed the severity of the new swine flu strain against seasonal flu strains and compared their ability to transmit from infected to non-infected ferrets via respiratory droplets.

Lead MIT author Dr Ram Sasisekharan, the Edward Hood Taplin Professor and director of the Harvard-MIT Division of Health Sciences and Technology (HST) and senior microbiologist at the CDC Dr Terrence Tumpey had already discovered that the severity of a flu infection depends on the ability of the hemagglutinin protein in the virus to bind to a particular type of receptor on the surface of human respiratory cells.

For this study, they compared the new swine flu strain to several seasonal flu strains, including some mild ones and the extremely severe 1918 strain that killed millions worldwide.

As expected, they found that the new swine flu strain was able to bind to the human respiratory tract umbrella-shaped alpha 2-6 glycan receptor. They reported that:

"In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets."

But, binding efficiency also depends on how well the virus can attach to the human respiratory tract receptor, and here they found that the receptor binding site in the hemagglutinin protein of the new swine flu virus was not as effective at binding to the human receptor as the other flu viruses.

Sasisekharan said:

"While the virus is able to bind human receptors, it clearly appears to be restricted."

The weak or restricted binding ability, together with a genetic variation in the H1N1 RNA polymerase enzyme PB2 that MIT scientists reported in Nature Biotechnology nearly a month ago, explains why the virus does not spread as readily as seasonal flu, he added.

(A virus uses RNA polymerase to control replication once it has infected a host. The MIT group found that new H1N1 strain does not have the version of the PB2 gene necessary for efficient transmission).

But this is no reason to be relaxed, since we know that flu viruses can mutate quickly, and one such mutation may improve ability of the new swine flu virus to attach to the human respiratory tract receptor. If that happens, then it will spread much more easily.

"We need to pay careful attention to the evolution of this virus," says Sasisekharan.

To test how easily the new strain spreads, Sasisekharan and colleagues put ferrets in close contact with each other and also kept apart. In close contact the virus particles spread from ferret to ferret easily, for instance when they touched each other. When they were kept further apart, so that transmission could only be via airborne respiratory droplets, the infection spread less readily.

Sasisekharan said this was consistent with what we have seen in humans, where most outbreaks have occurred in limited clusters, such as in a family or school, but not much further outside of that.

Another reason to keep an eye on the evolution of this new virus is that the MIT researchers working on the PB2 study also found that the virus is only one mutation step away from a version that would interact weakly with the antiviral Tamiflu (oseltamivir), raising the possibility that Tamiful resistant strains of swine flu may easily emerge.

In the second study, Dr Ron. A M Fouchier a virologist with the Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues also found, using ferrets, that the new A(H1N1) virus was more pathogenic than a seasonal A(H1N1) virus, "with more extensive virus replication occurring in the respiratory tract".

However, when they looked at transmission from ferret to ferret, they found that transmission via aerosol or respiratory droplets was equally efficient in the new swine flu virus as the seasonal flu virus, which differs markedly from the result of the other study.

They concluded that:

"These data suggest that the 2009 A(H1N1) virus has the ability to persist in the human population, potentially with more severe clinical consequences."

"Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice"
Taronna R. Maines, Akila Jayaraman, Jessica A. Belser, Debra A. Wadford, Claudia Pappas, Hui Zeng, Kortney M. Gustin, Melissa B. Pearce, Karthik Viswanathan, Zachary H. Shriver, Rahul Raman, Nancy J. Cox, Ram Sasisekharan, Jacqueline M. Katz, and Terrence M. Tumpey.
Science, Published online 2 July 2009.
DOI: 10.1126/science.1177238

"Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in Ferrets."
Vincent J. Munster, Emmie de Wit, Judith M. A. van den Brand, Sander Herfst, Eefje J. A. Schrauwen, Theo M. Bestebroer, David van de Vijver, Charles A. Boucher, Marion Koopmans, Guus F. Rimmelzwaan, Thijs Kuiken, Albert D. M. E. Osterhaus, and Ron. A. M. Fouchier.
Science, Published online 2 July 2009
DOI: 10.1126/science.1177127

Source: Science, Massachusetts Institute of Technology.

Written by: Catharine Paddock, PhD


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