[Kabar-indonesia] NS: Key stage to dengue fever replication found

[Joyo at aol.com]

New Scientist magazine
Issue 2563 / August 4, 2006

Key stage to dengue fever replication found

By Roxanne Khamsi

The discovery that the dengue fever virus needs to
bend into a circle in order to replicate suggests new
ways to treat this and similar diseases, including
West Nile virus and encephalitis, say researchers.
Future drugs that prevent the virus from forming a
ring shape could one day save thousands of lives, they
add.

“The challenge now is to see if we can design a small
molecule to do the job,” says Andrea Gamarnik at the
Leloir Institute in Buenos Aires, Argentina.

There are about 50 million cases of dengue fever
globally each year, the World Health Organization
estimates. The virus is spread through the bite of the
Aedes aegypti mosquito and claims around 25,000 lives
each year, many of them children. There is no
treatment or vaccine available for the disease, which
is dubbed “break-bone fever” due to the terrible pain
it inflicts.

Gamarnik and her colleagues say they have found the
key to the virus’s replication – and that this could
be its Achilles’ heel.

It was discovered only recently that the virus, made
of RNA, can change its shape from a long strand into a
circle. It is able to do so thanks to special, short
sequences on the ends of the strands that attract one
another, acting like “sticky tape”, according to the
researchers. But the importance of this shape was not
clear.
Promoter region

Now Gamarnik has discovered that the particular viral
enzyme required to replicate the virus is only able to
recognise a ring-shaped structure. When the dengue
strand forms a circle, proteins can latch on to the
“promoter” region at the joined ends of the strand
and, crucially, go on from there to replicate the
virus, Gamarnik explains.

The team tested their theory using animal cells. When
the sticky ends of the strand were modified not to
match, the virus failed to replicate in mosquito or
hamster cells. However, when these modified ends were
re-engineered to attract one another again in a new
way, the virus succeeded in replicating within the
cells.

The new findings should encourage researchers to look
for molecules that either block the sticky ends from
attaching or block the protein from binding to the
promoter region, says Gamarnik. She believes such
molecules could one day serve as powerful drugs to
treat patients with dengue fever.

And Gamarnik adds that other illnesses, such as West
Nile disease, caused by the same group of viruses as
Dengue fever, known as “flaviviruses”, may be tackled
with a similar approach. She says that West Nile virus
appears, for example, to have similar sticky ends,
though no one has yet shown it adopting a circular
shape to replicate.

Journal reference: Genes and Development (DOI:
10.1101/gad.1444206)

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Joyo Indonesia News Service
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