Solving a longstanding scientific puzzle, researchers at the University of Illinois at Chicago have not only discovered how the body’s first line of defense against dangerous microbes inadvertently helps HIV rapidly infect the human immune system.
They’ve filmed the process as well.
In a remarkable series of movies created with images from time-lapse microscopy, UIC microbiologists Thomas Hope and David McDonald have documented how HIV enters human T cells, where it multiplies with abandon and eventually subverts the entire immune system, causing AIDS.
The movies show how HIV co-opts the very mechanism the body has evolved to defend itself against such pathogens.
“A picture is worth a thousand words,” Hope said, quoting a colleague at a recent scientific meeting. “A video is worth a million.”
The paper detailing the findings was accepted for publication in Science less than two weeks ago and was rushed to print in the May 1 online version of the journal called Science Express, which highlights scientifically important and newsworthy studies.
In the early stages of any infection, the dendritic cells of the immune system — the first responders — spring into action. These are the “garbage men of the body,” as Hope calls them, constantly patrolling the neighborhood, looking for garbage to clean up.
Normally, when the dendritic cells find a piece of garbage — a virus or other pathogen — they pick it up and degrade it into tiny bits. They then show those bits to the T cells, alerting these executives of the garbage company to the potential danger.
The dendritic cells do this by making physical contact with the T cells, forming a tight interface, called an immunological synapse, through which the cells talk to one another via molecular signals.
If they make the right connection, the T cells then mobilize the rest of the immune system, sending out the trucks — other immune cells — to hunt for the garbage that the dendritic cells spotted, destroy the material, and save the body from disease.
While dendritic cells pick up HIV, however, they don’t destroy all the virus. Instead, scientists recently discovered, they inadvertently encourage infection, somehow helping HIV more rapidly infect the T cells.
McDonald said the “somehow” has now been answered.
Using a fluorescent dye that makes HIV particles glow green, Hope and McDonald photographed living dendritic cells with HIV particles inside. When the cells made contact with other cells, the HIV particles began streaming toward the juncture.
Not only that, but certain surface proteins on T cells necessary for infection by HIV also moved to the point of contact.
Further images clearly showed HIV particles transferring from the dendritic cells into the T cells through that same site — the “infectious synapse,” as the researchers call it.
Just as the immunological synapse signals the start of the immune response, so the infectious synapse jump-starts infection.
“HIV exploits the dendritic machinery for its own ends, taking advantage of the cells’ special relationship with T cells to gain entry and launch its assault,” McDonald said. “Moreover, HIV doesn’t get destroyed in the process.”
“What viruses do is try to find weak points in the immune system and take advantage of them,” Hope said. “It’s a billion-year-old war: the body builds defenses against viruses, and the viruses find ways to thwart those defenses.”
The researchers are particularly excited about their finding because it may apply to other pathogens. Recent studies have shown that Ebola virus, cytomegalovirus and the bacterium that causes tuberculosis all hitch rides on the dendritic cells just as HIV does.
“These pathogens appear to have discovered the same weak point in the immune system and exploited it,” Hope said. “If true, then we may have discovered an important target for therapies that would combat not just HIV but many infectious diseases.”
Other researchers involved in the study were Li Wu and Vineet Kewalramani of the National Cancer Institute and Stacy Bohks and Derya Unutmaz of Vanderbilt University.
For more information about UIC, visit www.uic.edu.