Blocking Regulatory Immune System Proteins May Help Combat HIV

Beneficial effects seen in blocking the immune response against HIV.

Temporarily blocking type 1 interferon, combined with the use of antiretroviral therapy (ART), may restore immune function and speed up viral suppression against HIV, according to a study published in the Journal of Clinical Investigation. The study is the first to demonstrate the role type 1 interferon plays in driving the body’s immune destruction during HIV infection, according to the authors.

“This findings is completely counterintuitive, because many believe that the more interferon at work, the better,” said investigator Scott Kitchen. “We show that the type of interferon being produced during chronic stages of HIV infection has detrimental effects on the body’s ability to fight off HIV and other types of infection or cancer, and could actually be contributing to accelerated HIV disease.”

The investigators wanted to block type 1 interferon in order to reduce chronic activation of the immune cells, allowing the exhausted CD8 T cells to restore their abilities to fighting strength.

The investigators used mouse models that had their immune systems replaced with human immune system cells, thymus tissue, and bone marrow. The HIV-infected mice were treated with antibodies that blocked type 1 interferons, so that their immune systems could revert from a state of exhaustion, according to the study.

This process allowed the immune system to produce sufficient amounts of CD8 T cells that sought to attack and kill HIV-infected cells. When combined with ART, the treatment accelerated the effect of ART in suppressing HIV, according to the study.

“We found—–counterintuitively––that blocking this immune response against the virus had beneficial effects in lowering the amounts of virus and increasing the ability of the immune response to clear out the virus,” Kitchen said.

The authors noted that although the findings are not definitive, they offer a proof of principle in a humanized mouse system.

“This could have profound implications for the development of therapies that include such approaches as interferon alpha therapy,” said lead investigator Anjie Zhen. “This shows that a proper balance is required when administering this type of therapy, where too much can have detrimental effects in suppressing important immune responses.”

More experiments are needed in non-human primates before moving on to human clinical trials, the authors concluded.