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!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy