Researchers at the University of Hawaii and Oregon Health Sciences University have identified a new cellular pathway that could be used to help eliminate, not just suppress, HIV in patients infected with the virus.

A research team led by Lishomwa Ndhlovu of the UH John A. Burns School of Medicine and OSHU’s Jonah Sacha isolated a receptor on T-cells that compromises the ability of these immune cells to control and eliminate HIV.

The study was published in the current issue of the scientific journal PLoS Pathogens.

Combination antiretroviral drugs have proved effective in suppressing HIV in patients. However, if a patient stops taking the drugs, the dormant virus rapidly reasserts itself.

An immune system cell called CD8+ Killer T-cell exerts some initial control over the virus, even without drugs, but these cells eventually wear down.

“A preponderance of emerging evidence indicates that the functions of the HIV-specific CD8+ Killer T-cells are severely compromised and enters a state of ‘exhaustion,’ rendering the cells less effective at eliminating HIV-infected cells,” Glen Chew, lead author of the study and a doctoral candidate in immunology at the medical school, explained in a statement Jan. 11.

The researchers found that two so-called “negative immune checkpoint receptors” — TIGIT and PD-1 — were associated with HIV progress and were present in exhausted T-cells. TIGIT was also active in simian immunodeficiency virus in rhesus macaque primates used in laboratories.

The researchers reasoned that by interfering with the TIGIT and PD-1 pathways, they could rejuvenate exhausted CD8+ T-cells, which could then be used to eliminate HIV in blood.

The discovery has significant implications for the proposed “shock and kill” strategy of eliminating dormant HIV.

Scientists have speculated that “shocking” infected cells with agents that awaken the dormant HIV virus would allow the immune system to then recognize and “kill” the virus. The problem has been that exhausted CD8+ T-cells are too weak to eliminate the reactivated virus.

However, rejuvenating the exhausted cells by blocking TIGIT and PD-1 pathways could empower the immune system to destroy HIV in the blood, they said.