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one quick bite, a tiny mosquito bred in the lingering rainwater
in a discarded tire or crushed beer can, can infect a human with
the potentially fatal dengue virus. The virus’ potentially lethal
complication, dengue hemorrhagic fever, infects as many as 100 million
people annually, and the Centers for Disease Control and Prevention
calls dengue the most important mosquito-borne viral disease affecting
humans today. And although the disease is largely tropical, the
United States is far from immune: dengue outbreaks have been reported
in Texas, Hawaii and the southeastern United States.
But recently, Children’s researchers discovered a method
that can potentially block the protein that helps the virus develop
into the shape that allows it to infect cells. This discovery may
shorten the race to find a dengue cure, and scientists are confident
it will help them better understand the lethal implications of the
virus. The findings were reported in the Procedings of the National
Academy of Sciences in May. Stephen
Harrison, PhD, Howard Hughes investigator, was senior author
of the study.
The dengue virus is so threatening because of its ability
to bypass the human body’s first layer of defense, the cell membrane.
The dangerous E protein, which forms the harmful shape of the virus,
folds itself into a fist-like shape and punches a hole through the
protective membrane of a cell, allowing the virus to enter, replicate
itself and spread to other cells. The E protein achieves its virulent
effects by stretching, bending and ultimately dumping its viral
genes into a cell. The researchers discovered a pocket in the protein
that could prevent the formation of that dangerous shape. If the
pocket can be filled with a drug to prop the protein open, the virus
may not be able to fuse or infect healthy cells.
“Inhibiting fusion is a sensible way of inhibiting viral
replication,” says Harrison “This may turn out to be a false lead,
but it suggests an interesting avenue to screen for compounds to
inhibit dengue fusion.” The study’s implications go beyond dengue
and may yield advances in treating yellow fever, tick-borne encephalitis,
Japanese encephalitis and other types of viruses. The study is part
of a new initiative at Harvard Medical School, known as the Center
for Molecular and Cellular Dynamics, in which Harrison and other
researchers are looking for meaningful ways to integrate their growing
understanding of genes, proteins, and molecular structures into
a better overall understanding of human health and disease.—ZB
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