Dengue Virus

Classification
Dengue is a term for a group of illnesses caused by four viruses, which are extremely relevant because they can infect
humans. The dengue viruses belong to the flavivirus family, which are positive strand RNA viruses (ssRNA). The viruses
are known as DENV 1, DENV 2, DENV 3, and DENV 4. The primary vector of transmission is one of two types of
mosquitos, Aedes aegypti and Aedes albopictus.

Taxonomy
 Family: Flaviviridae
 Genus: Flavivirus
 Species: Dengue virus

Morphology

Spherical, 40–60 nm in diameter. Genome: positive-sense, single-stranded RNA, 11 kb in

size. Genome RNA infectious. Envelope. Three structural polypeptides, two glycosylated.
Replication: cytoplasm. Assembly: within endoplasmic reticulum. All viruses serologically
related.

Structure
 E Protein
Envelope proteins are on the surface of the dengue virion and play a key role in cell entry; the structure of the
protein will affect the way that the virus can interact with the host cell. The dengue virus consists of the genome
and nucleocapsid, which is the genetic material and surrounding proteins, contained within a viral envelope made
of lipids. The viral envelope anchors multiple proteins including the E protein. Being a flavivirus, dengue enters the
host cell by means of receptor-mediated endocytosis, meaning that the virus binds to receptor proteins on the cell
to induce a conformational change that allows entry.

E proteins play a vital role in the dengue lifecycle by allowing the virus to enter host cells. As such, changes to the
E protein may influence the course of the virus. The E proteins undergo conformational changes during
endocytosis, and targeting the proteins may prove to be an effective antiviral strategy agains dengue. Although
current research illuminates many new aspects about the role of E proteins, the specific mechanisms by which they
function is still being elucidated.

 Envelope Protein Variation

E protein structure varies between the four types of dengue and between individual strains of the same type. This
variation manifests as changes in protein sequence due to genomic changes, as well as in three-dimensional
structural differences. It is unclear the mechanism by which changing the envelope protein changes the
pathogenicity of DENV strains, but strains with different degrees of pathogenicity often have differing E proteins.

- Sequence Variation
The sequence of the dengue virus envelope protein has been shown to vary strain to strain, but a direct link
between sequence variation and pathogenesis has not been found.

A study looked at properties of the dengue virus, such as the E protein, that affect their degree of pathogenicity.
Specifically, the authors looked at factors that determined whether the infection would manifest as dengue fever
or dengue hemorrhagic fever.
 - Structural Variation
Differing sequences of envelope proteins can affect their conformational arrangements, which in turn may alter
their functionalities.

The four different types of dengue virus have slightly different genomes, which means that they may have
different protein structures because the genomic sequence for an E protein will alter the amino acid sequence
and the folding of the protein. Antibodies that neutralize one type of dengue virus may be ineffective against
another dengue strain due to these structural differences so understanding structural differences is key to
treating the virus. Crystallography can show the folded structure of the proteins and allow for comparison of
proteins from the different strains. Modis and collaborators used crystallography to learn about the structure of
DENV 3 E protein and compare it to the previously characterized analogue in DENV 2.

Virulence factors
The virus that causes dengue fever has four different serotypes DEN-1, DEN-2, DEN-3, and DEN-4. These serotypes
have the same genome and morphology but different antigens. Being infected by one serotype will lead to lifelong
immunity to that serotype only and does not protect against other serotypes. Because of the genetic variation between
the viral strains it is possible for a person to be infected with all four different serotypes at different times during their life.

Replication