Bringing Structure to Biology
Dengue Virus: A Trojan Horse of the Molecular World
The image for June in our 2018 calendar depicts the Dengue Virus (DENV). This virus is responsible for dengue fever, a disease found in low-income populations within tropical areas within Africa, Asia, and the Americas.
Dengue Virus is found primarily in the tropics because the virus is transmitted by tropical mosquitos, and it affects around 50 to 100 million people each year. When a mosquito carrying dengue virus bites a person, the virus enters the blood together with the mosquito's saliva. It binds to, and enters cells of the immune system. The immune cells respond by producing a number of signaling proteins that evoke an immune response, such as cytokines and interferons. It is this reaction that is responsible for many of the symptoms, such as headaches, and muscle, joint, and bone pain, also fever and skin rashes. In severe cases, the virus weakens the blood system and can lead to hemorrhages, the fluid from the bloodstream leaks through the wall of small blood vessels into body cavities leading to less blood circulating in the blood vessels, and the blood pressure drops so low that insufficient blood is supplied to the body’s vital organs.
There are five antigenically different serotypes of Dengue Virus called DENV-1 to DENV-5. Infection with the virus induces the production of immunoglobulin G (IgG) antibodies, described as homotypic. These provide lifelong immunity, but only against the specific dengue serotype (hence homotypic). If a person is infected a second time with a different dengue serotype, the infection can exhibit an effect known as antibody-dependent enhancement. Antibodies are made that bind to, but do not neutralize, the virus. This allows it to behave as a "trojan horse” as the virus is delivered by the antibodies to cell have ingested the virus for destruction in a still viable state. Upon ingestion the virus is activated by the acid environment of the phagosome and begins to replicate. As a result of the antibody-dependent enhancement, a second infection, even years later, can be much more severe than the initial one, if the two infections are by two different viral serotypes.
Dengue virus is an RNA virus that has a genome that encodes only ten proteins. Three of these are structural proteins that both form the outer coat (capsid) of the virus particle (eg PDB entry 3j6 shown above) and have a role in the delivery of the RNA genome into host cells. The remaining seven proteins are involved in the production of new viruses once the virus is inside the host cell. The three dimensional structures of many of these can be found in the PDB: Explore Dengue virus in the PDB.
The image to the left is an artwork by Smilla Heaney, from Impington Village College in Cambridge. She has used the technique of silk Batik to capture the beauty and symmetry of this virus (PDB 4cct). In this technique hot wax is dropped onto the silk, before applying dyes, leaving a distinct white outline, from the absence of dye, in the silk when the wax is removed.