Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Changes in amino acids in the 1918 influenza virus cut transmission

06.02.2007
Modest changes in the 1918 flu virus's hemagglutinin receptor binding site—a molecular structure critical for the spread of infection—stopped viral transmission in ferrets, according to a new study conducted by researchers at Mount Sinai School of Medicine and at the Centers for Disease Control and Prevention.

The finding, published in the February 1 issue of Science, could have significant clinical implications in helping scientists develop ways to break the disease cycle and possibly help reduce the risk for a potential pandemic.

While flu pandemics occur every 10 to 40 years, the factors that lead to the emergence of pandemic viruses are not well understood, explains study co-author Adolfo García-Sastre, PhD, Professor of Microbiology at Mount Sinai School of Medicine. "What's most threatening is the possibility of another pandemic, similar to that of 1918, which was caused by a novel influenza subtype virus capable of causing severe respiratory disease and death," says Dr. García-Sastre. "So if we can understand the molecular mechanisms behind its transmission, perhaps we can do something to block transmission and prevent illness."

To do this, Dr. García-Sastre and his team studied two key molecular structures: hemagglutinin, a protein located in of the surface of the influenza virus, and sialic acid, a cellular molecule that is recognized by hemaglutinins of both human and avian strains of influenza virus. These molecules are key to initiation of infection. There are 16 different subtypes of hemagglutinin called H1 through H16, present in influenza virus strains circulating in birds. H1 and H3 are found today in human influenza viruses.

Hemaglutinin helps open the door to the cell to allow the virus to infect. The first step is in this process is the binding of the hemagglutinin to sialic acid containing molecules in the cell surface. There are two primary ways sialic acids are associated with molecules in the cell surface—one is through an alpha-2,6 bond and another is through an alpha-2,3 bond. Hemagglutinins from avian influenza virus prefer binding to alpha 2-3 sialic acids, while hemagglutinins from human influenza viruses prefer binding to alpha 2-6 sialic acids, which are highly abundant in the upper respiratory tract of humans. For an avian virus to be able to jump to humans and to start a new pandemic, it has been hypothesized that the hemagglutinin needs to mutate and change its binding preference from alpha2-3 to alpha2-6 sialic acids.

In this study, the researchers used ferrets as an animal model of human influenza virus infection, due to the presence of alpha2-6 sialic acids in the respiratory tract of ferrets, similar to the human scenario. Groups of ferrets were infected with three types of influenza viruses; two from existing viral strains related to the 1918 flu and taken from human tissue, and the third, which was artificially created in a laboratory and made to look like avian flu. One virus bound to only alpha-2,6, the second bound to both, and the artificially-generated virus bound to only alpha-2,3.

The researchers were surprised to discover that the ferrets infected with all three viruses, including the one with preference for binding to alpha2-3 sialic acids, experienced severe disease, with high levels of virus replication in the respiratory tract. However, only the virus with specificity for binding to alpha2-6 silaic acids was able to transmit by aerosols to contact ferrets. "It appears that when the virus only had an alpha-2,3 binding activity, replication and virulence didn't change," explains Dr. García-Sastre. "These animals still had symptoms, however transmission was practically abolished." Since the artificially-generated virus featured alpha-2,3 sialic acid binding activity, this finding indicated that alpha-2,6 sialic acid binding activity was more important for optimal viral transmission. "Our findings indicate that, to become more transmissible in humans, the currently circulating avian influenza H5N1 virus requires a receptor binding change in the hemagglutinin to a predominant alpha-2,6 sialic acid binding preference," Dr. García-Sastre adds. "Although this is likely not to be the only change required by H5N1 viruses to become transmissible in humans, this could help us make more accurate predictions on the ability of an influenza virus to transmit among humans and unravels the existence of molecular determinants of transmission that could be used as targets for the development of novel drugs that will stop influenza virus transmission, and therefore, help to stop epidemics and pandemics of influenza."

Mount Sinai Press Office | EurekAlert!
Further information:
http://www.mssm.org

More articles from Health and Medicine:

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>