Scientists have discovered a way to block replication of the most common form of HIV at a key moment when the infection is just starting to develop.
Transmitted through bodily fluids, the HIV-1 virus infects and destroys key immune cells, known as CD4 T cells, that would ordinarily mount a defense against the virus and initiate the antiviral activity of other immune cells.
Scientists have long known that a substance produced by CD4 T cells called Interleukin-21 (IL-21) plays an important role in the immune system by activating immune cells that specialise in killing viruses like HIV-1 and driving the production of antibodies that attack them.
However, it was unclear how IL-21 might affect the early stages of HIV-1 infection that allows the virus to grow and spread unabated soon after a person is exposed.
Researchers from Weill Cornell Medical College, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University conducted two studies to uncover this effect.
The researchers created a culture from human tissues, primarily spleen and lymph node tissue. After exposing the cells to IL-21, they introduced HIV-1 and found that after 72 hours, cultures with IL-21 contained more than two-thirds less virus than those that didn’t receive the treatment.
The second model tested IL-21 in mice transplanted with human stem cells to create a physiological environment as close as possible to that in people.
Over the course of two weeks, the mice began producing IL-21. After 14 days, more than half of the mice with IL-21 did not display a detectable level of HIV-1.
An analysis of the results suggested that IL-21 not only jump starts the immune system but also stops the HIV-1 virus from replicating during a critical, early window of its development, when it is concentrated in one location and has not yet started to spread throughout the body.
“This study highlights components of the human immune system that are capable of mounting an antiviral response and driving intrinsic resistance to HIV-1,” said senior author Dr Laurie H Glimcher, of Weill Cornell Medical College.
“We are hopeful that this knowledge will help bring us one step closer to shielding patients from this deadly and complex virus,” Glimcher said.
The reduction in viral load is due to the cascade of events initiated by IL-21.
The investigators found that IL-21 instructs CD4 T cells to increase the amount of a small RNA molecule. That molecule, microRNA-29 (miR-29), inhibits the replication of HIV-1, limiting the amount of virus produced from infected cells.
“Our study has uncovered a potentially potent arsenal that patients have against the virus. We think IL-21 is one of those arsenals and that deploying it early will be very powerful in fighting the infection,” said lead author Dr Stanley Adoro, a postdoctoral associate in medicine in Glimcher’s lab.