Effects of Pathogen-Vector Interactions on the Transmission of Dengue Virus

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Effects of Pathogen-Vector Interactions on the Transmission of Dengue Virus

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A Viral Biorealm page on the family Effects of Pathogen-Vector Interactions on the Transmission of Dengue Virus

Dengue Virus

Figure 1. Electron micrograph of dengue virus (DENV).[1]



Group IV: ss(+)RNA virus
Family: Flaviviridae
Genus: Flavivirus

Figure 2. Main vector of dengue virus, Aedes aegypti or the Asian tiger mosquito.[2]


Dengue virus (DENV) is the causative agent of both classical dengue fever, and the more severe manifestations; dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS)[3]. It is most commonly transmitted by the mosquito vector Aedes aegypti but can be transmitted by other members of the genus Aedes including Aedes albopictus (Figure 2)[4]. There are four different serotypes of dengue virus (DENV 1-4). Infection with one serotype affords life-long immunity to that serotype but only partial (heterologous) immunity to other serotypes for a short period of time post-infection. After initial protective immunity the risk of developing DHF or DSS upon reinfection strain from a different serotype increases.

This increased risk for severe dengue is the result of antibody-dependent enhancement of viral infection. Host heterotypic non-neutralizing antibodies from previous DENV infection bind DENV virions. After recent DENV infection there are enough antibodies to neutralize any new dengue viruses but overtime the number of neutralizing antibodies drops. At some point there are so few enough antibodies left that upon reinfection with a new strain the anitbodies can bind but not nuetralize the virus. The constant region of the antibody can go on to bind a FcγR receptor on the surface of a number of different types of immune cells.Normally when a pathogen-antibody complex binds to a FcγR receptor a cytoxic or phagocytoic response initiated by the immunne cell. DENV somehow avoids this response and is brought close enough to its host cell receptor it can bind and infect the cell as seen in figure 3.

Figure 3. Antibody-dependent enhancement of DENV infection. [2]


The FcγR receptors are effect in controlling other pathogens but DENV has evolved to exploit this pathway. The FcγR receptor is not needed for DENV entry but does increase infectivity DENV and allows the virus display cell tropisms not seen in primary DENV infection. With more cells infected more viroins are produced leading to higher levels of viremia in the blood which is correlated with increased risk for DHF and DSS. increase infectivity of the virus in immune cells by increasing overall viral load within the patient which in turn increases the risk of DHF and DSS [source?]

Within serotypes dengue viruses are organized by genotypes, subtypes, clades, variants, groups and finally strains [3]. The large number of dengue strains in the world combined with only partial crossover immunity to other strains makes concurrent (multi-strain) infections or reoccurring dengue infections possible (just like repeated bouts of the flu), especially in areas with high prevalence of DENV.

Dengue viruses are now endemic in many tropical parts of the world putting about a third of the world’s population at risk of infection. There are estimated to be over one hundred million new infections per year and rising [4,5]. Rising rates of infection are the result of reduced multiple factors that affect vector population and range. vector control in areas that need it most has been cutback and global warming has expanded vector ranges to areas previously DENV free. Milder winters at higher latitudes are allowing adult and larvae mosquitoes to survive longer into the fall and return earlier in the spring allowing the DENV transmission cycle to continue throughout a greater part of the year than in the past. DENV is becoming a threat to industrialized nations once thought to be too far away from the tropics for Dengue fever to be a threat. In the U.S. the number of indigenous dengue cases is rising. In Brownsville Texas, 25% of the residents who had never traveled outside the united states had antibodies indicating prior exposure to a strain of DENV that had to have been maintaining a transmisssion cycle in that are for quite some time [discover article][6].

The severity of dengue infection also continues to increase. The ratio of dengue DHF and DSS cases to classical dengue fever have increased dramatically over the past sixty years. It has become the leading cause of hospitalization and death in children in several endemic countries [6].

Dengue Hemorrhagic Fever


Figure 3. Ecchymosis (bleeding under the skin) associated with dengue hemorrhage fever.[5]


Although classical dengue is not usually fatal it has very high morbidity; its alternate name is break-bone fever for the severe joint pain during infection. Disease is most common in infants, young children, and adults. Classical dengue manifests itself with a mild to high fever, red rash, debilitating headaches, muscle and joint pain.

The more severe manifestations of the disease are dengue hemorrhage fever and dengue shock syndrome. Young children and those previously infected with dengue are most at risk for these complications from dengue infection [4]. Dengue shock syndrome results when plasma leaks out of capillaries as a result of infection of the endothelial cells lining blood vessels [see DHF thing]. This leads to edema (swelling of tissue because of fluid escaping the circulatory system), abdominal pain (as a result of the edema) and hypotension (low blood pressure resulting from a drop in total blood volume from fluid loss). Oxygen and nutrients stop reaching the bodies tissues because of inadequate circulation of the blood as a result of these symptoms and this can lead to shock and death [5]. Dengue hemorrhage fever occurs when normal blood coagulation is disrupted by infection. Fever, emesis (vomiting), and hemorrhaging (bleeding) are all symptoms common to this type of dengue [5]. The results of internal hemorrhaging can be seen in the form of tiny red spots (petechiae) or sometimes patches under the skin as well as bloody stool (feces) and bleeding from the gums and nose (Figure 3)[4]. Mortality from these complications can be up to 14% without proper care [3].

Figure 1. Beware of the Bite; poster warning residents to avoid mosquito bites in areas with high prevalence of dengue fever.[1]



Unfortunately there are no anti-viral drugs for dengue. The only treatment is supportive care in the form of fluid replacement and pain management [4]. With no licensed vaccine, The spread of dengue is currently controlled by halting disease transmission.

Controlling the transmission of dengue virus is simple but labor-intensive and costly. Vector control is the main way dengue transmission is curbed. In the past heavy pesticides such as DDT were used to wipe out mosquitoes but this has fallen out of favor as the toxic effects on the environment became known. Now prevention transmission is centered on public health education programs that urge residents to get rid of standing water in and around their homes and seek treatment if they have dengue fever-like symptoms. Both public health programs and large scale vector control rely on government funding and both have been pushed aside over the years to pay for other things. Researchers are trying to understand the complexities of dengue virus replication in mosquito vectors because of its overreaching effects on the epidemiology of the disease [4].

Figure ?. Simplified epidemiological triad for dengue virus transmission. Note the number of factors that influence DENV replication in mosquito vector.



Coinfection of the mosquito vector with multiple DENV strains or the bacterium Wolbachia/ and interactions between DENV and the vector’s immune system all modulate viral replication within the vector. With a better understanding of how each of these factors affects the overall viral load and rate of viral replication with in the mosquito vector it will be possible to come up with better strategies for vector transmission control and prevention as well as the mitigation of future DENV epidemics (figure DENV triangle).