Potential Cure for HIV Discovered: Researchers Identify Kill Switch for Inactive HIV

Potential Cure for HIV Discovered: Researchers Identify Kill Switch for Inactive HIV

Human Immunodeficiency Virus (HIV) infection used to be a death sentence; however today, thanks to antiretroviral therapy, patients with HIV can live long and healthy lives without developing acquired immune deficiency syndrome (AIDS).

Despite more than three decades of research there is still no cure for HIV infection. Drugs can be taken to keep HIV in the body dormant and thus prevent the immune system from being attacked, but HIV reservoirs remain in the body and will be reawakened and will rapidly multiply if treatment is stopped.

Now, researchers at the University of California San Diego have identified a potential cure for HIV – One which appears to kill off the reservoirs of dormant HIV and will prevent reactivation and replication in the event that medications are stopped.

The ‘kill switch’ for HIV discovered by the researchers plays a key role in HIV reproduction in immune cells. Turn that switch off or delete it entirely and HIV medications would no longer be required, as the reservoirs of dormant HIV would be eradicated.

“The most exciting part of this discovery has not been seen before. By genetically modifying a long noncoding RNA, we prevent HIV recurrence in T cells and microglia upon cessation of antiretroviral treatment, suggesting that we have a potential therapeutic target to eradicate HIV and AIDS.” said Tariq Rana, PhD, professor of pediatrics and genetics at UC San Diego School of Medicine.

Rana and his team conducted the first first genome-wide expression analysis of long noncoding RNA (lncRNA) in HIV-infected macrophages. Macrophages are immune cells that promote inflammation and stimulate the immune system to rid the body of foreign invaders. Typically, RNAs encode proteins, but IncRNAs instead switch genes on and off inside cells.

The researchers identified one IncRNA they named HIV-1 Enhanced LncRNA (HEAL), which is found in high levels in individuals infected with HIV. The HEAL gene is believed to be a fairly recent addition to the human genome, and one which is upregulated by HIV-1 infection of monocyte-derived macrophages, microglia, and T lymphocytes.

The researchers used a combination of approaches to silence the gene along and the CRISPR-Cas9 gene editing tool to remove the HEAL gene entirely. Both approaches prevented HIV from recurring once treatment with retroviral drugs stopped in their in vitro studies.  The researchers are now moving on to studies in animal models.

“Our results suggest that HEAL plays a critical role in HIV pathogenesis,” explained Rana. “Further studies are needed to explain the mechanism that leads to HEAL expression after an individual is infected by HIV, but this finding could be exploited as a therapeutic target.”

The study is detailed in the paper – The Long Noncoding RNA HEAL Regulates HIV-1 Replication through Epigenetic Regulation of the HIV-1 Promoter– which was recently published in the journal mBio. DOI: 10.1128/mBio.02016-19.

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