Multiple viral diseases are spread through vectors, like ticks and mosquitoes, resulting in massive health care issues and epidemics worldwide. My question has always been, "if the vectors are infected with the virus, are they getting a disease? And what is in it for the host organism? What is driving the vector to spread the viral infection?"
George Dimopoulous’ group at Johns Hopkins University shed light on these questions in their latest publication on Dengue virus and the effect on its main vector, mosquito species Aedes aegypti.
A (more than brief) summary on Dengue virus (DENV):
DENV infects over 100 million people yearly, and more than one-third of the world’s population (2.5 billion, to be exact) is living in areas at risk for transmission (www.cdc.gov/dengue/).
Though DENV is listed as a tropic and subtropic illness, it is clear from the map that the Northern hemisphere is being closed in on, and that the “flood line,” which generally indicates where Aedes aegypti are present, is ever-rising. Unfortunately for the US, mosquitoes cannot be stopped at the border.
DENV transmission begins with a DENV-infected person. This person will have virus circulating in their blood (viremia) for 4-5 days. During this period, an uninfected Aedes aegypti mosquito bites the infected human, ingesting DENV-infected blood. Within the mosquito, DENV replicates within the midgut epithelium and subsequently spreads through the hemolymph to replicate in the fat body and trachea. WIthin 1-2 weeks, it spreads to the salivary glands. Next, the infected mosquito bites another susceptible human and transmits the virus to that person, along with every other human that it bites for the rest of its life.
Of note, vertical, or mosquito-to-mosquito, transmission has been reported; however, mosquitoes mainly acquire DENV by feeding on the blood of an infected human.
DENV seems to have a pretty active life in the mosquito. What is happening in there?
What we do know is that infection of the salivary gland is particularly important for the transmission of DENV. Mosquito salivary gland produces numerous anti-coagulants (to let the blood flow freely), anti-inflammatory proteins and vasodilatory proteins (for better ease in probing and collecting blood from humans), and its immune system reduces viral and bacterial loads in the human blood that is ingested.
Additionally, mosquito saliva can induce an anti-inflammatory immune reaction in the host, most likely in the event that the human cannot detect the bug on their arm sucking their blood, but this can also increase the viremia levels, increasing the chance of infection.
Is there any antiviral defense in the salivary gland?
Interestingly, mosquitoes possess a potent immune system, capable of responding to many microbes – but most groups have studied the effect of DENV in the midgut, not the salivary gland.
In order to gain a better understanding of how DENV was affecting the salivary gland, Dimopoulous’ group did an amazing, yet relatively simple, experiment: They looked at gene expression in non-infected A. aegypti salivary glands and DENV-infected A. aegypti salivary glands to identify genes affected by DENV infection.
In this approach, they used whole-genome microarray-based analyses to compare the transcript levels in both types of salivary glands. Their results suggested a “broad impact of DENV infection on a variety of salivary gland functions, including those implicated in immunity, host-seeking, and blood acquisition”. Yes, this means that DENV is controlling the immune response and BEHAVIOR.
To break it down:
Indeed, they did find that A. aegypti mount an antiviral immune response in the salivary glands during DENV infection. This is very cool.
Most interestingly (to me, but probably to you as well), was that two genes they found that were over-expressed during infection of DENV in the salivary glands, were odorant-binding proteins (OBP) that affect host-seeking and blood-feeding – meaning, the virus is controlling mosquito behavior through regulation of chemosensory genes! This is amazing.
Separately from this microarray, they specifically silenced these two genes and found that there was increased probing initiating (host-seeking behavior) and probing times, “indicating less efficient feeding behavior”.
This is preliminary data on viral control of behavior genes; however, what an intriguing finding! I can’t think of a virus that induces behavioral changes in humans except H1Z1…
Shuzhen Sim, Jose L. Ramirez, George Dimopoulos (2012). Dengue Virus Infection of the Aedes aegypti Salivary Gland and Chemosensory Apparatus Induces Genes that Modulate Infection and Blood-Feeding Behavior PLoS Pathogens, 8 (3), 1-15