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Dengue viruses are spread by mosquitos and can cause a deadly hemorrhagic fever or a milder illness. This lesson covers the differences between the types dengue viruses and how they cause disease.

Dengue Viruses

In many parts of the world, mosquitos are nothing more than a nuisance. Their bites can cause us to get itchy, red bumps, and they’ve ruined many a backyard barbecue. But in some cases, mosquitos can cause even more damage.

Some viruses, like Dengue viruses, are spread to humans by insects like mosquitoes and ticks. These viruses are members of the Flavivirus genus. Other well-known Flaviviruses include West Nile and yellow fever. Dengue viruses are spread by mosquitos in tropical areas of the world and cause about 100 million cases of illness each year.

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Immune Response to Dengue

There are four different types of dengue viruses. They are divided into serotypes, which are distinct variations of a virus or bacteria, based on how they are recognized by the immune system. Dengue virus 1 (DEN-1) was first discovered in Japan in the 1940s. The other three viruses, DEN-2, DEN-3, and DEN-4, are closely related to DEN-1, but are not recognized as the same virus by the immune system.This means if you get infected with DEN-3, your immune system will produce antibodies that recognize only DEN-3. These antibodies will protect you from being infected with DEN-3 again.

However, if are later bitten by a mosquito carrying DEN-1, the DEN-3 antibodies won’t protect you from getting infected. These antibodies may actually make the disease be much more severe than the first time you had dengue. While this strange phenomenon is not completely understood, scientists think that your immune response may help the virus to spread and lead to more severe symptoms.

Dengue Fever and Dengue Hemorrhagic Fever

The first time a person is infected with a dengue virus, they usually have a milder form of the disease called dengue fever. The typical symptoms are fever, headache, joint and muscle pain, and a rash.

There are no specific treatments for dengue fever, though medication can be used to control the fever and pain. This painful illness is also known as breakbone fever, but typically less than 1% of people die from it.

Patient with dengue fever rash
Patient with rash from dengue fever

A second infection with a different serotype can lead to a much more severe disease known as dengue hemorrhagic fever. This form of the illness also occurs much more frequently in children and infants. At first, the symptoms are very similar to dengue fever and can last from two days to a week.

As the fever gets better, the person then starts to have severe vomiting and abdominal pain. Their capillaries, which are the smallest blood vessels in the body, start to leak causing bleeding internally and bleeding from the skin, nose, and gums. If untreated, these serious complications can cause a person to go into shock or circulatory failure and die. A person with dengue hemorrhagic fever should be cared for in a hospital and given fluids to keep them stabilized.

With proper treatment, the mortality rate is only 2 to 5%, but without treatment the mortality rate can be as high as 50%.

Viral Structure

Dengue viruses are round in shape and covered in a viral envelope. This envelope comes from the membrane of an infected human cell and is covered with two viral proteins: E and M. These proteins help the virus attach to and infect human skin cells.

Inside of the envelope is the viral genome coated by C protein, which forms a nucleocapsid. The viral genome is a single piece of single-stranded RNA. Instead of making each viral protein separately, this RNA is translated by the host cell to form a polypeptide, or long protein strand. The individual viral proteins are made by cutting up the polypeptide into smaller pieces.

This process makes all ten of the viral proteins dengue virus needs to replicate, including the other nonstructural viral protein (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).

Electron micrograph showing dengue viruses (cluster of dark spheres) outside of a cell
Electron micrograph of dengue viruses

Viral Replication

Infection starts with the E protein recognizing and binding to a human cell. This binding triggers the cell to fold in its membrane around the virus, forming a bubble known as an endosome. As the endosome moves deeper into the cell, it is acidified, which lets the viral membrane fuse with the endosome membrane. This releases the viral nucleocapsid into the cytoplasm.The virus then uses the cell’s endoplasmic reticulum to start making viral proteins.

The endoplasmic reticulum is a cell structure composed of tubes of membrane and ribosomes, which carry out the translation of mRNA into protein. The viral RNA genome has the same structure as the cell’s messenger RNA (mRNA), and this tricks the cell into making viral proteins.Several dengue viral proteins are used to reorganize the endoplasmic reticulum into what are known as cytoplasmic viral factories.

The cell begins making more viral protein and viral RNA, which are packaged together to form new viruses. The new viruses are released at the cell surface and can infect other cells or spread to a new host.

Lesson Summary

Dengue viruses are divided into four serotypes based on how they are recognized by the immune system. Most infections cause a relatively mild form of illness called dengue fever.

Being infected with one serotype of dengue virus does not protect you from being infected with another serotype. A second infection is actually thought to lead to a more severe and lethal illness known as dengue hemorrhagic fever. Dengue viruses have a complex viral life cycle that hijacks the cell’s endoplasmic reticulum.

The infected cell then makes all the proteins encoded by the viral RNA genome, allowing the virus to replicate.

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