Washington: Scientists, including one of Indian-origin, have discovered a human protein that forces latent HIV out of hiding, and poisons the virus on its way out, an advance that could help cure the disease and prevent relapse when medication is stopped.
The ultimate impediment to a cure for human immunodeficiency virus (HIV) infection is the presence of latent, HIV-infected cells, which can reawaken and produce new virus when antiretroviral drug therapy is stopped.
These cells are untouched by antiretroviral therapy and are unseen by the immune system. Moving medicine closer to a cure for HIV, scientists at Blood Systems Research Institute (BSRI), the University of California at San Francisco (UCSF) and the University of Hawaii in the US discovered that the human sugar-binding protein galectin-9 potently forces latent HIV out of hiding, and poisons the virus on its way out.
Researchers used cutting-edge technologies to demonstrate that galectin-9, a beta-galactoside-binding lectin, reactivates latent HIV and renders infected cells visible to the immune system.
This concept of therapeutically forcing latent HIV out of hiding as a curative approach is known as the “shock and kill” HIV eradication strategy.
“For nearly two decades, antiretroviral therapy has demonstrated efficacy in suppressing HIV replication, but these drugs do not completely clear viral infection or fully restore health,” said Satish Pillai, Associate Investigator at BSRI.
“We need a means to draw out the virus from its hidden reservoirs within the body and allow the body’s own immune system to eliminate it,” Pillai said.
Beyond subjecting latent HIV-infected cells to destruction by the immune system, researchers found that galectin-9 strongly increases levels of an antiviral protein called “APOBEC3G” in infected cells.
APOBEC3G is a lethal mutagen that destroys the genetic code of viruses including HIV. This ensures that virus that comes out of hiding at the hands of galectin-9 will be sterilized on its way out of the cell, preventing any further infection.
The findings show that galectin-9 is a new weapon in the HIV cure arsenal, promoting eradication of the latent HIV reservoir in infected individuals on antiretroviral therapy.
Researchers also found that galectin-9 works by manipulating sugars on the surface of HIV-infected cells to deliver the signals that force latent HIV out of hiding.
“Galectin-9 binds to certain classes of sugars on the surface of cells to start a chain reaction that forces HIV out of hiding,” said Mohamed Abdel-Mohsen, Scientist at BSRI and UCSF School of Medicine.
“This sugar coating may hold the key to new therapeutics that can be harnessed to cure HIV and possibly a range of other infectious diseases,” he said.
The research was published in the journal PLOS Pathogens.