- Hello, Jeff
- "The hemagglutinin (HA) structure from the Viet04
virus was found to be closely related to the 1918 virus HA, which caused
some 50 million deaths worldwide."
- Dr. Henry Niman told us this over a year ago on your
- Minor Mutations In Avian Flu Virus
Increase Chances Of Human Infection
Scripps Research Institute
Contact: Keith McKeown
- Few adaptations are needed to transform it into a potential
- The H5N1 avian influenza virus, commonly known as "bird
flu," is a highly contagious and deadly disease in poultry. So far,
its spread to humans has been limited, with 177 documented severe infections,
and nearly 100 deaths in Indonesia, Vietnam, Thailand, Cambodia, China,
Iraq, and Turkey as of March 14, 2006, according to the World Health Organization
- "With continued outbreaks of the H5N1 virus in poultry
and wild birds, further human cases are likely," said Ian Wilson,
a Scripps Research professor of molecular biology and head of the laboratory
that conducted the recent study. "The potential for the emergence
of a human-adapted H5 virus, either by re-assortment or mutation, is a
clear threat to public health worldwide."
- Of the H5N1 strains isolated to date, the researchers
looked at A/Vietnam/1203/2004 (Viet04), one of the most pathogenic H5N1
viruses studied so far. The virus was originally isolated from a 10-year-old
Vietnamese boy who died from the infection in 2004. The hemagglutinin (HA)
structure from the Viet04 virus was found to be closely related to the
1918 virus HA, which caused some 50 million deaths worldwide.
- Using a recently developed microarray technology-hundreds
of microscopic assay sites on a single small surface-the study showed that
relatively small mutations can result in switching the binding site preference
of the avian virus from receptors in the intestinal tract of birds to the
respiratory tract of humans. These mutations, the study noted, were already
"known in [some human influenza] viruses to increase binding for these
- The study was published on March 16, 2006 by ScienceXpress,
the advance online version of the journal Science.
- Receptor specificity for the influenza virus is controlled
by the glycoprotein hemagglutinin (HA) on the virus surface. These viral
HAs bind to host cell receptors containing complex glycans-carbohydrates-that
in turn contain terminal sialic acids. Avian viruses prefer binding to
?2-3-linked sialic acids on receptors of intestinal epithelial cells, while
human viruses are usually specific for the ?2-6 linkage on epithelial cells
of the lungs and upper respiratory tract. Such interactions allow the virus
membrane to fuse with the membrane of the host cell so that viral genetic
material can be transferred to the cell.
- The switch from ?2-3 to ?2-6 receptor specificity is
a critical step in the adaptation of avian viruses to a human host and
appears to be one of the reasons why most avian influenza viruses, including
current avian H5 strains, are not easily transmitted from human-to-human
following avian-to-human infection. However, the report did suggest that
"once a foothold in a new host species is made, the virus HA can optimize
its specificity to the new host."
- "Our recombinant approach to the structural analysis
of the Viet04 virus showed that when we inserted HA mutations that had
already been shown to shift receptor preference in H3 HAs to the human
respiratory tract, the mutations increased receptor preference of the Viet04
HA towards specific human glycans that could serve as receptors on lung
epithelial cells," Wilson said. "The effect of these mutations
on the Viet04 HA increases the likelihood of binding to and infection of
susceptible epithelial cells."
- The study was careful to note that these results reveal
only one possible route for virus adaptation. The study concluded that
other, as yet "unidentified mutations" could emerge, allowing
the avian virus to switch receptor specificity and make the jump to human-to-human
- The glycan microarray technology, which was used to identify
the mutations which could enable adaptation of H5N1 into the human population
in the laboratory, could also be used to help identify new active virus
strains in the field by monitoring changes in the receptor binding preference
profile where infection is active, according to according to Jeremy M.
Berg, the director of the National Institute of General Medical Sciences
(NIGMS), part of the National Institutes of Health (NIH). The glycan microarray
was developed by The Consortium for Functional Glycomics, an international
group led by Scripps Research scientists and supported by the NIGMS.
- "This technology allows researchers to assay hundreds
of carbohydrate varieties in a single experiment," Berg said. "The
glycan microarray offers a detailed picture of viral receptor specificity
that can be used to map the evolution of new human pathogenic strains,
such as the H5N1 avian influenza, and could prove invaluable in the early
identification of emerging viruses that could cause new epidemics."
- Other authors of the study include James Stevens of Scripps
Research; Ola Blixt of Scripps Research and Glycan Array Synthesis Core-D,
Consortium for Functional Glycomics; Terrence M. Tumpey, Influenza Branch,
Division of Viral and Rickettsial Diseases, Centers for Disease Control
and Prevention; Jeffery K. Taubenberger, Department of Molecular Pathology,
Armed Forces Institute of Pathology, and; James C. Paulson, Scripps Research
and Glycan Array Synthesis Core-D, Consortium for Functional Glycomics.
- The work was supported by the National Institute of Allergy
and Infectious Disease, the National Institute of General Medical Sciences
and the National Institutes of Health.
- About The Scripps Research Institute
- The Scripps Research Institute, headquartered in La Jolla,
California, in 18 buildings on 40 acres overlooking the Pacific Ocean,
is one of the world's largest independent, non-profit biomedical research
organizations. It stands at the forefront of basic biomedical science that
seeks to comprehend the most fundamental processes of life. Scripps Research
is internationally recognized for its research into immunology, molecular
and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular,
and infectious diseases, and synthetic vaccine development. Established
in its current configuration in 1961, it employs approximately 3,000 scientists,
postdoctoral fellows, scientific and other technicians, doctoral degree
graduate students, and administrative and technical support personnel.
- Scripps Florida, a 364,000 square-foot, state-of-the-art
biomedical research facility, will be built in Palm Beach County. The facility
will focus on basic biomedical science, drug discovery, and technology
development. Palm Beach County and the State of Florida have provided start-up
economic packages for development, building, staffing, and equipping the
campus. Scripps Florida now operates with approximately 160 scientists,
technicians, and administrative staff at 40,000 square-foot lab facilities
on the Florida Atlantic University campus in Jupiter.
- Patricia A. Doyle, DVM, PhD
Bus Admin, Tropical Agricultural Economics Univ of West Indies
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