Researchers have discovered a key step in how the dengue virus
infects a cell. The finding will allow researchers to study the
process in the laboratory and provide a valuable tool
for testing new drugs to prevent or treat infection.
Image courtesy of James Gathany, CDC.
The virus that causes dengue is transmitted by mosquitoes.
Dengue fever usually starts with a fever, joint pain, rash and
nausea. Without treatment, the virus can cause damage to blood
and lymph vessels and lead to dengue hemorrhagic fever, which
is marked by difficulty breathing, bruising and bleeding from
the nose, gums or under the skin. Each year, the virus infects
up to 100 million people and kills about 22,000, most of them
To infect a cell, the dengue virus initially binds to the cell
surface. It gains entry into the cell when it becomes enveloped
by the cell membrane during the creation of a pouch-like structure
known as an endosome. The virus waits inside the endosome until
it has traveled deep within the cell; then, it fuses its membrane
with the endosomal membrane and forms a pore through which it
releases its genetic material. Once inside the fluid interior
of the cell, the virus begins to reproduce itself.
Researchers have studied viral fusion in the laboratory at the
cell surface or by using artificial cell membranes. However,
attempts to fuse dengue virus under either of these conditions
have been unsuccessful. The reason for the lack of fusion has
puzzled researchers for years. A research team led by Dr. Leonid
V. Chernomordik at NIHs Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) set out to investigate
how the dengue virus fuses with its target membranes.
The researchers tagged dengue virus and cell membranes with
fluorescent probes that glow when the virus and membranes fuse.
Viral samples were also exposed to artificial membranes to
identify factors that allow fusion to occur. The study was funded
by NICHD and NIHs National Institute of Allergy and Infectious
The results appeared in the October 7, 2010, issue of PLoS
Pathogens. The researchers discovered that 2 conditions
are essential for dengue virus fusion. The first is an acidic
environment—a fundamental characteristic of endosomes.
The second is the presence of negatively charged lipids in
the endosome membrane, which are present only after an endosome
has been taken deep within the cell.
"The confluence of acidity and a negative charge deep in
the cell's interior ensures that the virus is safe within the
endosome early in its journey, when it is most vulnerable, but
can release its genome when it reaches its destination," Chernomordik
"We spent several years trying to understand how the dengue
virus fuses with its target membrane," Chernomordik says. "The
findings will now enable us to test new ways to disrupt the fusion
process and prevent infection."