Researchers at Johns Hopkins have modified HIV in a way that makes it no longer able to suppress the immune system. Their work, they say in a report published online September 19 in the journal Blood, could remove a major hurdle in HIV vaccine development and lead to new treatments.
"Something about the HIV virus turns down the immune response, rather than triggering it, making it a tough target for vaccine development," says David Graham, Ph.D., assistant professor of molecular and comparative pathobiology and medicine. "We now seem to have a way to sidestep this barrier," he adds.
Typically, when the body's immune system cells encounter a virus, they send out an alarm by releasing chemicals called interferons to alert the rest of the body to the presence of a viral infection. When the immune cells encounter HIV, however, they release too many interferons, become overwhelmed and shut down the subsequent virus-fighting response.
The researchers had learned from other studies that when human immune cells (white blood cells) are depleted of cholesterol, HIV can no longer infect them. It turns out the coat that surrounds and protects the HIV viral genome also is rich in cholesterol, leading the Johns Hopkins team to test whether viruses lacking cholesterol could still infect cells at all.
The researchers treated HIV with a chemical to remove cholesterol from the viral coat. Then they introduced either the cholesterol-diminished or normal HIV to human immune cells growing in culture dishes, and measured how the cells responded. The cells exposed to cholesterol-diminished HIV didn't release any initial-response interferons, whereas the cells exposed to normal HIV did.
"The altered HIV doesn't overwhelm the system and instead triggers the innate immune response to kick in, like it does with any first virus encounter," says Graham.
Next, the researchers checked to see if cholesterol-diminished HIV activates s
|Contact: Vanessa McMains|
Johns Hopkins Medical Institutions