Blocking mTor could thwart HIV replication in the gut

Electromicrograph showing an HIV-infected T cell in blue and yellow
HIV can hide and replicate in T cells. Canadian researchers believe they've found a way to cut down on these viral reservoirs.

Antiretroviral therapy has revolutionized the treatment of HIV, reducing viral loads in most patients to the point where the illness is not detectable in blood. Problem is, HIV can hide in immune cells called CD4 T cells, creating reservoirs that allow the virus to survive and replicate. Researchers at the University of Montreal Hospital Research Centre say they’ve discovered a way to block this replication in the stomach—thwarting the virus and cutting down on the inflammation that viral reservoirs cause.

The key is inhibiting a naturally occurring molecule called mTOR—a mechanism that’s already being used to treat diabetes and some cancers. The researchers used existing mTOR-blocking drugs to study what would happen in colon cells taken from HIV patients whose viral load was undetectable. The drugs “significantly reduced HIV replication,” according to a press release.

CD4 T cells possess a marker on their surface called CCR6, which instructs them to travel to the gut. Using colon biopsies taken from HIV patients who are taking antiretroviral therapy, the researchers discovered that cells expressing CCR6 also contain high amounts of mTOR. That’s when they decided to give the mTOR-blocking drugs a try. The results were published in the journal JCI Insight.

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The most widely used mTOR inhibitor in cancer is rapamycin, a drug that was originally developed to prevent organ rejection. Analogs of the drug have been approved to treat some cancers and are under investigation in others. In May, startup Aadi Bioscience raised $23 million to develop an mTOR inhibitor to treat a rare form of sarcoma. The best known mTOR inhibitor in diabetes is metformin, which is widely used to treat the Type 2 form of the disease.

Although current HIV treatments have greatly improved the prognosis for patients, searching for a cure is still a priority. In September, a startup called Excision BioTherapeutics attracted some buzz when it raised a $10 million seed round to fund human trials of a technology that uses the gene-editing technique CRISPR to eliminate latent HIV.

Using mTOR inhibitors in HIV patients wouldn’t just cut down on viral reservoirs, the University of Montreal researchers suggest, but it might also improve the quality of life for patients. "In specifically targeting CD4 T cells carrying the CCR6 molecule, which contains dormant HIV, we think these medications will decrease gastrointestinal inflammation,” said Petronela Ancuta, a professor there, in the release.