Although many diseases infect the body and overpower the immune system with speed and sheer force, the dengue virus seems to take a different approach, according to new Duke research.
Christopher Nicchitta, professor of cell biology and biochemistry and associate professor of pathology, is the senior author of a recent study showing how the virus covertly replicates in humans without triggering the immune system. The trick to evading detection, his team showed, is for the virus to hide and stealthily overtake a major protein production site for the cell, called the endoplasmic reticulum.
“[Dengue] is a very real health problem,” Nicchitta said. “After billions of viruses and hundreds of millions of years, it has evolved to where it replicates very slowly to accomplish its goal of spreading.”
Dengue—a lethal virus with no medical cure—has a slow-replicating, tiny genome that can lead to excruciatingly painful symptoms in patients.
This virus spans over Central and South America, regions of Africa and South Asia and has become more common in United States territories of the past few years, according to the Centers for Disease Control and Prevention. Due to increased temperatures from global warming, the region in which the mosquitoes that carry dengue inhabit is expanding, consequently increasing the virus's range. Part of this global expansion has included urban centers, Nicchitta noted.
“The mosquito that carries the virus is very well adapted to live in urban environments,” he said. "This is the easiest way to transfer the disease—in a very crowded place.”
The danger with this virus is that it replicates inside the host cells of the body undetected until it becomes large enough to cause problems. By the time the body notices its invader, the virus has already multiplied and infected the host.
“It is sort of the perfect Trojan horse,” Nicchitta said. "It goes in, slowly takes over, emergency sensing systems aren’t turning on, and the protein sensing networks aren’t seeing a problem.”
Apart from the symptoms that are associated with dengue fever, the virus is also a menace for its variability, he noted. With four serotypes—which are variations of the virus—it has the ability to infect a host more than once.
“If you contract a different serotype of dengue, your immune system will now recognize it...the antibodies produced by your immune system will bind to the dengue virus and actually help it get into cells,” Nicchitta said.
Pathogens such as the virus associated with chickenpox lead to an immune reaction such that secondary exposure to a similar virus typically does not lead to serious infection. However, with dengue, he said, a secondary infection is accompanied by a much more severe immune response and can lead to death.
There is currently no cure for the virus. Although a vaccine designed to prevent dengue once existed, the supposed cure did more harm than good, Nicchitta explained.
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He added that the group's findings could one day lead to stopping the virus in its tracks.
“We are really interested in understanding how it is not turning on [the body’s] stress sensors,” Nicchitta said. “Maybe this is just a general strategy, and if it is, then we want to figure that out, understand how it is able to do that and see if there is a way to therapeutically disrupt that.”