>> Dengue virus is an RNA virus.
Its outer surface is covered
with envelope proteins surrounding a lipid
bilayer envelope.
Inside the envelope is a capsid shell
that contains the virus's RNA genome.
Immune cells are targeted by the dengue virus.
There are two cell surface receptor molecules important
in dengue infection.
The cognate receptor is involved in normal infection
and the FC receptor is involved
in a phenomenon called antibody-dependent enhancement.
The virus's envelope protein binds to the cognate receptor
and triggers a cellular process called
receptor-mediated endocytosis.
The virus is internalized in a bubble-like
structure called the endosome.
When endosomes form,
proton pumps lower the pH of the interior.
The virus responds to the lowered pH
by changing the conformation of the envelope proteins
to form spike-like structures.
The tips of the spikes are hydrophobic, which allows them
to penetrate the endosome's membrane.
They bend until the endosome's membrane
and the virus's membrane fuse together
and release the capsid into the cytoplasm.
The capsid breaks apart and releases the viral RNA.
The viral RNA travels to the rough endoplasmic reticulum.
It is a positive-sense strand
and can be directly translated into proteins.
The ends of the RNA form structures that bind
to translation initiation proteins.
The complex attaches to the ribosome
to initiate translation.
The whole viral genome is translated as a single,
long, poly-protein chain.
The capsid protein is on the cytoplasm side
of the endoplasmic reticulum.
The envelope protein and the pre-membrane protein are
in the lumen side and are activated
by the host's peptidase enzyme.
In the cytoplasm, one of the viral proteins,
a protease enzyme, activates all the other proteins
in a poly-protein chain.
These proteins aggregate
to form the RNA replication complex.
The viral RNA is synthesized in multiple steps.
First, the ends of the viral RNA fold up,
and the RNA forms a circle.
The RNA then attaches to the replication complex
to start the first round of synthesis.
Using the virus's positive- sense RNA as the template,
a negative-sense copy is made.
The pair of RNA strands forms a double helix.
The RNA then becomes a circle again.
This time, the negative-sense strand acts as a template
to make a positive-sense strand.
Many copies of the positive-sense RNA are made
by repeated cycles of RNA synthesis.
Some of these strands are translated
to make more viral proteins.
Eventually enough proteins are made to assemble new viruses.
The envelope proteins aggregate in the lumen
of the endoplasmic reticulum
and the capsid proteins aggregate
on the cytoplasmic side.
A viral RNA binds to the capsid protein and is packaged
into a new virus particle as it buds off
into the endoplasmic reticulum.
The virus is still immature.
Its pre-membrane proteins cover the tips
of the envelope proteins
to prevent premature fusion back into the cell.
The virus buds off and travels through the Golgi apparatus
and continues toward the cell's surface.
Before reaching the surface,
the pre-membrane protein is processed,
and the virus becomes mature.
New dengue viruses are released from the cell ready
to infect other cells.