HIV-AIDS: Following your gut

September 18, 2017
HIV (yellow) infecting a human immune cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Researchers at the University of Montreal Hospital Research Centre (CRCHUM) have discovered a way to slow viral replication in the gastrointestinal tract of people infected by HIV-AIDS.

This advance, published in JCI Insight, might well lead to the development of a new therapeutic strategy to supplement antiretroviral therapy (ART), improving the control of viral replication in HIV-infected persons and preventing complications associated with chronic infection.

"We have identified a molecule that stimulates HIV replication in CD4 T located in the gut," said Petronela Ancuta, a CRCHUM researcher and professor at UdeM. "We have also started testing medications to block this replication and decrease inflammation of the intestinal mucosa. This is a promising new approach to eradicate HIV, or at least to achieve functional cure."

The ART used to treat HIV-infected persons can decrease viral loads to often undetectable blood levels, and is effective in preventing evolution of the infection towards acquired immunodeficiency syndrome (AIDS). But HIV is tenacious. "In spite of the effectiveness of antivirals, it hides in specific immune system cells, the CD4 T cells, which harbour the virus and form viral 'reservoirs' in various peripheral tissues, particularly in the ," Ancula explained. "Inside these 'reservoirs,' some viral organisms continue to replicate, which leads to harmful inflammation in the gut. Hence the idea to limit at all levels and to counteract inflammation."

"The digestive tract is an environment conducive to viral 'reservoirs'," added the study's lead author, Delphine Planas, a CRCHUM doctoral candidate. "Our research demonstrates that CD4 T cells which migrate from the blood to the gut will be modified. En route, they acquire the tools that aid the virus in infecting them. Identifying these tools helps us understand why the gut represents a sort of sanctuary favourable to HIV, and thus how to combat these 'reservoirs'."

An HIV 'postal code'

CD4 T cells migrate from the blood to the gut thanks to marker molecules expressed on their surface; some of these, called CCR6, act like a "postal code" for the cells, indicating they should direct themselves to the gut. Previously, the researchers had shown that cells expressing the CCR6 molecule are preferential targets of in-vitro infection, and are viral "reservoirs" in subjects being treated with ART.

Using biopsies of the sigmoid colon and blood of HIV-infected persons on ART therapy, Ancuta's team, along with one led by Jean-Pierre Routy of the Research Institute of the McGill University Health Centre (RI-MUHC), has now discovered that in the colon, the CD4 T cells which express the CCR6 postal code also contain a large amount of another molecule called mTOR, an important regulator of metabolic mechanisms.

"It is the mTOR molecule which is in part responsible for the high vulnerability to HIV of the CD4 T lymphocytes expressing CCR6 and residing in the gut," explained Planas.

A potential treatment

By interfering with mTOR activity during in-vitro experiments with existing medications, researchers have been able to significantly reduce HIV replication in the cells of HIV-infected patients whose viral load was undetectable.

Medications inhibiting mTOR activity are used successfully in the treatment of cancer and diabetes. Other studies are needed to validate their use in the treatment of HIV-AIDS. But researchers already recognize the potential for improving quality of life and increasing chances of curing HIV-infected patients by using mTOR inhibitors to supplement antiretroviral treatments.

"In specifically targeting CD4 T cells carrying the CCR6 molecule, which contains dormant HIV, we think these medications will decrease gastrointestinal inflammation of individuals on ART," Ancuna said. "Over the long term, we hope that this type of treatment will reduce even more the amount of virus persisting in gut reservoirs. Therefore, this is an important strategy to cure HIV, and one that deserves to be tested."

Explore further: A new strategy reported to combat influenza and speed recovery

More information: Delphine Planas et al, HIV-1 selectively targets gut-homing CCR6+CD4+ T cells via mTOR-dependent mechanisms, JCI Insight (2017). DOI: 10.1172/jci.insight.93230

Related Stories

A new strategy reported to combat influenza and speed recovery

May 23, 2017
The influenza virus turns infected lung cells into factories that churn out thousands of copies of the virus to spread the infection. St. Jude Children's Research Hospital scientists have reported a promising new approach ...

Immune-enhancing treatment may destabilize HIV reservoirs

July 21, 2016
Although antiretroviral therapy (ART) can reduce the amount of HIV in the blood to an undetectable level in most chronically infected people, it cannot eliminate reservoirs of HIV that persist in latently infected immune ...

HIV 'safe houses' identified

July 14, 2016
Researchers from the University of Montreal Hospital Research Center (CRCHUM) have identified cells that provide "safe houses" for the human immunodeficiency virus (HIV) during antiretroviral therapy (ART).

Designed drug candidate significantly reduces HIV reactivation rate

July 8, 2015
HIV-infected patients remain on antiretroviral therapy for life because the virus survives over the long-term in infected dormant cells. Interruption of current types of antiretroviral therapy results in a rebound of the ...

Scientists zoom in on AIDS virus hideout

March 15, 2017
French scientists said Wednesday they had found a way to pinpoint elusive white blood cells which provide a hideout for the AIDS virus in people taking anti-HIV drugs.

Targeting dormant HIV

September 19, 2016
Discovery of a novel, advanced technique to identify the rare cells where human immunodeficiency virus (HIV) hides in patients taking antiretroviral therapy (ART). This is an important step forward in the search for a HIV/AIDS ...

Recommended for you

Study suggests a way to stop HIV in its tracks

December 1, 2017
When HIV-1 infects an immune cell, the virus travels to the nucleus so quickly there's not enough time to set off the cell's alarm system.

Discovery puts the brakes on HIV's ability to infect

November 30, 2017
Viewed with a microscope, the virus faintly resembles a pineapple—the universal symbol of welcome. But HIV, the virus that causes AIDS, is anything but that. It has claimed the lives of more than 35 million people so far.

Rising levels of HIV drug resistance

November 30, 2017
HIV drug resistance is approaching and exceeding 10% in people living with HIV who are about to initiate or reinitiate first-line antiretroviral therapy, according to the largest meta-analysis to date on HIV drug resistance, ...

Male circumcision and antiviral drugs appear to sharply reduce HIV infection rate

November 29, 2017
A steep drop in the local incidence of new HIV infections accompanied the rollout of a U.S.-funded anti-HIV program in a large East-African population, according to a study led by researchers at Johns Hopkins Bloomberg School ...

Combination HIV prevention reduces new infections by 42 percent in Ugandan district

November 29, 2017
A study published today in the New England Journal of Medicine provides real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections ...

Research on HIV viral load urges updates to WHO therapy guidelines

November 24, 2017
A large cohort study in South Africa has revealed that that low-level viraemia (LLV) in HIV-positive patients who are receiving antiretroviral treatment (ART) is an important risk factor for treatment failure.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.